82 results on '"Wright, Michael"'
Search Results
2. Bacterial second messenger cyclic di‐AMP in streptococci.
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Wright, Michael J. and Bai, Guangchun
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STREPTOCOCCUS , *CYCLIC adenylic acid , *BACTERIAL growth , *PHOSPHODIESTERASES - Abstract
Cyclic dimeric adenosine monophosphate (c‐di‐AMP) has been well studied in bacteria, including those of the genus Streptococcus, since the first recognition of this dinucleotide in 2008. Streptococci possess a sole diadenylate cyclase, CdaA, and distinct c‐di‐AMP phosphodiesterases. Interestingly, cdaA is required for viability of some streptococcal species but not all when streptococci are grown in standard laboratory media. Bacteria of this genus also have distinct c‐di‐AMP effector proteins, diverse c‐di‐AMP‐signaling pathways, and subsequent biological outcomes. In streptococci, c‐di‐AMP may influence bacterial growth, morphology, biofilm formation, competence program, drug resistance, and bacterial pathogenesis. c‐di‐AMP secreted by streptococci has also been shown to interact with the mammalian host and induces immune responses including type I interferon production. In this review, we summarize the reported c‐di‐AMP networks in seven species of the genus Streptococcus, which cause diverse clinical manifestations, and propose future perspectives to investigate the signaling molecule in these streptococcal pathogens. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Understanding the costs of co‐commissioning: Early experiences with co‐commissioning in Australia.
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Bates, Shona, Harris‐Roxas, Ben, and Wright, Michael
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HUMAN services ,TRANSACTION cost theory of the firm ,TRANSACTION costs ,ORGANIZATIONAL learning ,CAPACITY building ,COST - Abstract
Public services, such as health and other human services, are increasingly being delivered by third‐party providers (providers) under contract to public sector organisations (PSOs). While often advantageous to PSOs, this creates a fragmented service context which is difficult for consumers to navigate. Further, providers often deliver services under multiple contracts to multiple funders, with high reporting requirements, high administrative costs, and low operational sustainability. Policymakers have encouraged co‐commissioning—where PSOs come together to jointly commission services—to increase the efficiency and effectiveness of outsourcing. This article seeks to understand the costs of co‐commissioning in Australia, and consequently the enablers and barriers to co‐commissioning. This qualitative study is based on the early experiences of co‐commissioning by one of 31 Primary Health Networks (PHNs). Using transaction cost economics (TCE) theory, the study explains how the PHN started co‐commissioning services with other PHNs, before co‐commissioning with other types of organisations. The PHN also co‐commissioned relatively simple activities first, before moving on to more complex services. The insights provided using TCE theory help explain why co‐commissioning is initially complicated (and costly), requiring time to understand both the services to be commissioned and the governance requirements of each party involved. While initial transaction costs may be high when co‐commissioning, this may reflect organisational learning and capacity development costs ‐ therefore, costs are expected to reduce over time. Points for practitioners: Fragmentation in policy and funding also leads to fragmentation of human services and high costs to service providers.Co‐commissioning is where multiple funders pool funds and strategically commission services together.Co‐commissioning offers a way to reduce fragmentation and reduce costs to service providers, potentially offering better public value.Co‐commissioning can initially take time and resources to establish.Over time, as organisations learn, the cost of co‐commissioning reduces potentially offering benefits to funders, providers, and service users. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients.
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Nagai, Minako, Wright, Michael J., Ding, Ding, Thompson, Elizabeth D., Javed, Ammar A., Weiss, Matthew J., Hruban, Ralph H., Yu, Jun, Burkhart, Richard A., He, Jin, Cameron, John L., Wolfgang, Christopher L., and Burns, William R.
- Abstract
Background: Patients with pancreatic ductal adenocarcinoma (PDAC) and liver metastasis are treated with palliative chemotherapy, whereas similar patients with metastatic colorectal cancer are considered for aggressive surgery. Methods: Using an institutional database, PDAC patients undergoing liver resection for isolated metastasis were identified. Their overall survival (OS), treatment factors, and clinicopathological variables associated with survival were also evaluated. Results: Forty‐seven patients underwent curative‐intent surgery for metastatic PDAC to the liver between 2000 and 2019. Median OS was 21.9 months from diagnosis. Fourteen patients underwent unplanned resection of radiographically occult liver metastasis during pancreatectomy with median OS of 8.7 months. On the other hand, 29 patients received systemic chemotherapy followed by planned resection; this cohort had the most favorable prognosis following aggressive surgery with median OS being 38.1 months from diagnosis and 24.1 months from surgery. Preoperative chemotherapy (HR = 7.1; p =.002) and moderate to well differentiation of the primary tumor (HR = 3.7; p =.003) were associated with prolonged survival in multivariate analysis, whereas lymph node metastases, response to preoperative therapy, number of liver metastasis, and extent of liver surgery were not. Conclusions: In select patients with PDAC and isolated liver metastasis, curative‐intent surgery can result in meaningful survival. This aggressive approach seems most beneficial in patients following induction chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Successional dynamics of the cultivated kelp microbiome.
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Davis, Katherine M., Zeinert, Logan, Byrne, Allison, Davis, Jonathan, Roemer, Cosmo, Wright, Michael, and Parfrey, Laura Wegener
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LAMINARIA ,KELPS ,MACROCYSTIS ,NATURAL immunity ,SACCHARINA - Abstract
Kelp are important primary producers that are colonized by diverse microbes that can have both positive and negative effects on their hosts. The kelp microbiome could support the burgeoning kelp cultivation sector by improving host growth, stress tolerance, and resistance to disease. Fundamental questions about the cultivated kelp microbiome still need to be addressed before microbiome‐based approaches can be developed. A critical knowledge gap is how cultivated kelp microbiomes change as hosts grow, particularly following outplanting to sites that vary in abiotic conditions and microbial source pools. In this study we assessed if microbes that colonize kelp in the nursery stage persist after outplanting. We characterized microbiome succession over time on two species of kelp, Alaria marginata and Saccharina latissima, outplanted to open ocean cultivation sites in multiple geographic locations. We tested for host‐species specificity of the microbiome and the effect of different abiotic conditions and microbial source pools on kelp microbiome stability during the cultivation process. We found the microbiome of kelp in the nursery is distinct from that of outplanted kelp. Few bacteria persisted on kelp following outplanting. Instead, we identified significant microbiome differences correlated with host species and microbial source pools at each cultivation site. Microbiome variation related to sampling month also indicates that seasonality in host and/or abiotic factors may influence temporal succession and microbiome turnover in cultivated kelps. This study provides a baseline understanding of microbiome dynamics during kelp cultivation and highlights research needs for applying microbiome manipulation to kelp cultivation. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Solid Pseudopapillary Neoplasms of the Pancreas Across Races Demonstrate Disparities with Comparably Good Prognosis.
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Lin, Young-Jen, Burkhart, Richard, Lu, Tzu-Pin, Wolfgang, Christopher, Wright, Michael, Zheng, Lei, Wu, Han-Yu, Chen, Ching-Hsuan, Lee, Shin-Yi, Wu, Chien-Hui, He, Jin, and Tien, Yu-Wen
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RACE ,LYMPHADENECTOMY ,PANCREAS ,PROGNOSIS ,ASIANS ,PANCREATIC surgery ,PANCREATECTOMY - Abstract
Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare with low-grade malignancy and unclarified clinicopathological features. This study aimed to examine their characteristics and re-evaluate current treatments. Methods: Databases from three sources were screened for patients with SPNs. We compared the perioperative variables, clinical data, overall survival (OS), and prognostic factors for recurrence among the three corresponding cohorts. Results: We identified 286 patients diagnosed with SPNs between 1988 and 2020. Patients were mostly women (81%; median age: 38 years), and peak incidence was observed in women of 20–29 years of age. SPNs had a peak incidence in Asian men at 50–59 years of age (p = 0.002) and a delayed peak incidence in Asian women at 30–39 years of age (p < 0.001). Treatment strategies differed significantly across the institutions and included variations in the number of harvested lymph nodes and rates of vascular resection. Lymph node positivity was the only predictor of postoperative recurrence (odds ratio, 2.2; 95% confidence interval, 1.38–2.99; p = 0.007). Higher rates of lymphovascular invasion (p = 0.02), perineural invasion (p < 0.001), and R1 margin involvement (p < 0.001), as seen in one institution, did not result in poorer long-term survival in terms of the overall (p = 0.43), SPN-specific (p = 0.69), and recurrence-free survivals (p = 0.067). Conclusions: In contrast to previous findings that SPNs are prevalent in young women, a racial predilection for middle-aged Asian men and a delayed female peak incidence were noted. Parenchyma-preserving pancreatectomy may be an acceptable treatment. Non-radical surgery may be appropriate in patients with multiple comorbidities. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Environmental filtering of macroinvertebrate traits influences ecosystem functioning in a large river floodplain.
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Rideout, Natalie K., Compson, Zacchaeus G., Monk, Wendy A., Bruce, Meghann R., Hajibabaei, Mehrdad, Porter, Teresita M., Wright, Michael T. G., and Baird, Donald J.
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FLOODPLAINS ,WETLANDS ,SHORELINES ,INVERTEBRATE communities ,ECOSYSTEM health ,ECOSYSTEMS ,STRUCTURAL equation modeling - Abstract
The biodiversity–ecosystem function hypothesis postulates that higher biodiversity is correlated with faster ecosystem process rates and increased ecosystem stability in fluctuating environments. Exhibiting high spatiotemporal habitat diversity, floodplains are highly productive ecosystems, supporting communities that are naturally resilient and highly diverse.We examined linkages among floodplain wetland habitats, invertebrate communities and their associated traits, and ecosystem function across 60 sites within the floodplain wetlands of the lower Wolastoq | Saint John River, New Brunswick, using structural equation modelling and Threshold Indicator Taxa ANalysis.We identified key environmental filters structuring invertebrate communities, by linking increased niche differentiation through shoreline change, flood pulse dynamics, and macrophyte bed complexity with increased taxa and functional diversity.Examination of traits linked to ecosystem functions revealed that more resilient wetlands with balance between primary productivity and decomposition as carbon sources were associated with greater functional evenness and richness, while habitat patches with elevated decomposition rates had lower functional richness, reflecting a simplified, more disturbed habitat.While our more complex overarching SEM model was ultimately compromised by an overspecified number of pathways, our results nevertheless are indicative of a divergence between wetland and riverine ecosystems in their relationships linking biodiversity and ecosystem function, illustrating how to define ecosystem health in wetland habitats, and demonstrating how critical functions support healthy wetland habitats by providing increased resilience to disturbance. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Developmental delay and progressive seizures in 2‐month‐old child with diffuse MRI abnormalities.
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Mateos, Marion K, Birdi, Nikhil, Basu, Anna P., Wright, Michael, Joshi, Abhijit, Annavarapu, Srinivas, Jacques, Thomas S., Mitra, Dipayan, and Bailey, Simon
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DEVELOPMENTAL delay ,SEIZURES (Medicine) ,HUMAN abnormalities ,MAGNETIC resonance imaging ,MEDICAL research ,CAUDA equina - Published
- 2022
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9. The impact of COVID‐19 on chronic disease management in primary care: lessons for Australia from the international experience.
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Parkinson, Anne, Matenge, Sethunya, Desborough, Jane, Hall Dykgraaf, Sally, Ball, Lauren, Wright, Michael, Sturgiss, Elizabeth A, and Kidd, Michael
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- 2022
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10. Accurate Nodal Staging in Pancreatic Cancer in the Era of Neoadjuvant Therapy.
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Javed, Ammar A., Ding, Ding, Baig, Erum, Wright, Michael J., Teinor, Jonathan A., Mansoor, Daniyal, Thompson, Elizabeth, Hruban, Ralph H., Narang, Amol, Burns III, William R., Burkhart, Richard A., Lafaro, Kelly, Weiss, Matthew J., Cameron, John L., Wolfgang, Christopher L., and He, Jin
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PANCREATIC surgery ,NEOADJUVANT chemotherapy ,PANCREATIC cancer ,TUMOR classification ,LYMPHATIC metastasis ,PANCREATIC duct - Abstract
Background: Nodal disease is prognostic in pancreatic ductal adenocarcinoma (PDAC); however, optimal number of examined lymph nodes (ELNs) required to accurately stage nodal disease in the current era of neoadjuvant therapy remains unknown. The aim of the study was to evaluate the optimal number of ELNs in patients with neoadjuvantly treated PDAC. Methods: A retrospective study was performed on patients with PDAC undergoing resection following neoadjuvant treatment between 2011 and 2018. Clinicopathological data were extracted and analyzed. Results: Of 546 patients included, 232 (42.5%) had lymph node metastases. The median recurrence free survival (RFS) was 10.6 months (95% confidence interval: 9.7–11.7) and nodal disease was independently associated with shorter RFS (9.1 vs 11.9 months; p < 0.001). A cutoff of 22 ELNs was identified that stratified patients by RFS. Patients with N1 and N2 disease had similar median RFS (9.1 vs 8.9 months; p = 0.410). On multivariable analysis, ELN of ≥ 22 was found to be significantly associated with longer RFS among patients with N0 disease (14.2 vs. 10.9 months, p = 0.046). However, ELN has no impact on RFS for patients with N1/N2 disease (9.5 vs. 8.4 months, p = 0.190). Adjuvant therapy was associated with RFS only in patients with residual nodal disease. Conclusions: Lymph node metastases remain prognostic in PDAC patients after neoadjuvant treatment. Among N0 patients, a cutoff of 22 ELN was associated with improved RFS and resulted in optimal nodal staging. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Primary care is the ideal setting to promote COVID‐19 vaccination for children.
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Barnes, Katelyn, Hall Dykgraaf, Sally, de Toca, Lucas, Wright, Michael, and Kidd, Michael
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Delays related to caregiver COVID-19 vaccine hesitancy Vaccine hesitancy caused by concern or misunderstanding of COVID-19 risks and the benefits of vaccination may be best addressed in general practice. Effective solutions previously implemented to increase influenza vaccination could include co-administration of the COVID-19 vaccines alongside other accepted childhood vaccinations.[19] This could offer a more sustainable strategy that might improve awareness of timing and normalise childhood COVID-19 vaccines by providing them in the context of other accepted vaccines.[[14], [19], [26]] Owing to an already large role in both COVID-19 specific and all other childhood vaccinations, general practice will be key in implementing short and long term strategies to increase COVID-19 vaccine access for children and families. Primary care is the ideal setting to promote COVID-19 vaccination for children. [Extracted from the article]
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- 2022
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12. How prepared is Australian occupational therapy to decolonise its practice?
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Rudman, Megan Tirzah, Flavell, Helen, Harris, Courtenay, and Wright, Michael
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INDIGENOUS Australians ,WELL-being ,OCCUPATIONAL therapy education ,ACCREDITATION ,PATIENT participation ,HEALTH of indigenous peoples ,RESEARCH methodology ,LEADERSHIP ,INTERVIEWING ,COLLEGE teacher attitudes ,OUTCOME-based education ,CULTURAL competence ,ACTION research ,QUESTIONNAIRES ,THEMATIC analysis ,JUDGMENT sampling ,CURRICULUM planning ,ELDER care - Abstract
Introduction: Being culturally secure, respectful and responsive can mean occupational therapists can contribute to improving the health and wellbeing of Aboriginal and Torres Strait Islander peoples. New culturally responsive accreditation and competency standards provide an opportunity to decolonise the profession to enhance the cultural capabilities of graduates. The purpose of this study was to explore how well‐prepared Australian occupational therapy courses are to implement the new standards. Methods: The principles of participatory action research were applied. An initial survey with occupational therapy academic staff was used to inform questions for semi‐structured interviews. Semi‐structured interviews were conducted with 10 occupational therapy academics and occupational therapy accreditors. Interview data were thematically analysed. Findings: The four themes identified from the interviews were: occupational therapy profession drivers, effective leadership, community and Elder involvement, and course design and delivery. Conclusion: The new accreditation and competency standards are a promising step forward for the profession. However, the profession needs to be better prepared to decolonise Australian occupational therapy. A positive and culturally secure way forward is to engage Elders and other community members in learning experiences to build student, academic and practicing occupational therapist's cultural capability. Non‐Aboriginal and Torres Strait Islander leadership at all levels of the profession and within universities is crucial to establishing trusting, reciprocal relationships to support deep knowledge exchange. These relationships lay the foundation to build cultural capabilities and decolonise processes in the profession. [ABSTRACT FROM AUTHOR]
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- 2021
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13. Downregulation of 5‐hydroxymethylcytosine is an early event in pancreatic tumorigenesis.
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Fujikura, Kohei, Alruwaii, Zainab I, Haffner, Michael C, Trujillo, Maria A, Roberts, Nicholas J, Hong, Seung‐Mo, Macgregor‐Das, Anne, Goggins, Michael G, Roy, Sujayita, Meeker, Alan K, Ding, Ding, Wright, Michael, He, Jin, Hruban, Ralph H, and Wood, Laura D
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PANCREATIC intraepithelial neoplasia ,PRECANCEROUS conditions ,DOWNREGULATION ,NEOPLASTIC cell transformation ,GENETIC regulation - Abstract
Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma. 5‐hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten‐eleven translocation (TET) enzyme‐mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten‐eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (n = 118). The study cohort included representation of the full spectrum of precancerous lesions from low‐ and high‐grade pancreatic intraepithelial neoplasia (n = 95), intraductal papillary mucinous neoplasms (all subtypes, n = 129), intraductal oncocytic papillary neoplasms (n = 12), and mucinous cystic neoplasms (n = 144). 5hmC and TET1 were significantly downregulated in all types of precancerous lesion and associated invasive pancreatic ductal adenocarcinomas compared with normal ductal epithelium (all p < 0.001), and expression of 5hmC positively correlated with expression of TET1. Importantly, downregulation of both 5hmC and TET1 was observed in most low‐grade precancerous lesions. There were no clear associations between 5hmC levels and clinicopathological factors, thereby suggesting a common epigenetic abnormality across precancerous lesions. We conclude that downregulation of 5hmC and TET1 is an early event in pancreatic tumorigenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Serum concentrations of estriol vary widely after application of vaginal oestriol cream.
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West, Nèvine, Day, Richard, Graham, Garry, Wright, Michael, White, Christopher, Popovic, Gordana, and Moore, Kate Hilda
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ESTRIOL ,ESTRADIOL ,BLOOD sampling ,ESTRONE ,PHARMACOKINETICS - Abstract
Aims: The aim of this study was to establish the pharmacokinetic profile of serum oestriol (E3) concentrations over 24 h following application of vaginal E3 in chronic users (>12 weeks of E3 use). The interindividual and intraindividual differences before and after E3 were examined. Methods: Ten women participated. Vaginal cream was omitted for ≥36 h prior to the study days. Blood sampling was performed for E3, oestradiol and oestrone concentrations prior to cream application and at 1, 2, 3, 5, 8, 10, 12 and 24 h afterwards. In five women, all samples were repeated on a separate day. Results: E3 was absorbed rapidly in most women. Peak serum E3 concentration occurred around 2 h (range 1–5 h). The decline in E3 concentrations was also rapid: falling <100 pmol L−1 in six out of ten women within 8 h and returning to ≤ 10 pmol L−1 at 24 h in nine out of the ten patients. Interindividual variability for peak concentrations was considerable (mean 546 pmol L−1; 95% CI 349–743). Area under the concentration–time curve (AUC) values over a dosage interval also varied widely: mean 2145 pmol.h L−1; 95% CI 1422–3233. However, repeated measurements in the same woman were highly (peaks: ρ = 0.94) or moderately (AUC: P = 0.74) correlated. Conclusions: Postmenopausal E3 concentrations are negligible. Serum E3 concentrations of chronic users of E3 cream varied greatly; however, concentrations declined rapidly within 8 h, generally reaching 'postmenopausal' levels by 24 h. The basis for the variation between subjects needs further elucidation. Additional research is required to establish the safety of topical E3. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin.
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Schmocker, Ryan K., Wright, Michael J., Ding, Ding, Javed, Ammar A., Cameron, John L., Lafaro, Kelly, Burns, William R., He, Jin, Wolfgang, Christopher L., and Burkhart, Richard A.
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- 2021
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16. "If you don't speak from the heart, the young mob aren't going to listen at all": An invitation for youth mental health services to engage in new ways of working.
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Wright, Michael, Culbong, Tiana, Crisp, Nikayla, Biedermann, Britta, and Lin, Ashleigh
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MENTAL health services , *TORRES Strait Islanders , *YOUTH health , *COMMUNITY-based participatory research , *MENTAL health - Abstract
Aim: Aboriginal and Torres Strait Islander young people are more likely to experience mental health issues or end their life by suicide than non‐Aboriginal youth, but are less likely to access mental health services for support. Systemic change is required if mainstream youth mental health services are to be relevant and culturally secure for Aboriginal and Torres Strait Islander young people. Methods: Building Bridges (2017‐2019) is a three‐year participatory action research project being conducted in partnership with the Nyoongar community and three mainstream youth mental health services in Perth, Western Australia. The project involves Nyoongar Elders and Aboriginal and Torres Strait Islander young people working directly with senior management and key staff of youth mental health services to co‐design, implement and evaluate a framework for systems change. The aim of the project is to increase Aboriginal and Torres Strait Islander young people's engagement with services and improve mental health outcomes for young people and their families. Results: This paper outlines the engagement process that underpinned the first phase of the project. Our research methods are premised by an investment in establishing safe spaces for the Elders, young people and service staff to engage in open, honest dialogue. We present two key activities that illustrate this process of building trust and deepening understanding, namely: spending time "On Country" and engaging in a "storying" process. Conclusions: Building Bridges demonstrates the centrality of trusting relationships for systemic change and the way in which meaningful engagement is at the core of both the process and the outcome. [ABSTRACT FROM AUTHOR]
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- 2019
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17. Zinc oxide nanoparticles as contrast‐enhancing agents for microwave imaging.
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Lahri, Rachita, Rahman, Mohammed, Wright, Michael, Kosmas, Panagiotis, and Thanou, Maya
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BREAST cancer diagnosis ,MICROWAVE imaging in medicine ,SINGLE walled carbon nanotubes ,NANOMEDICINE ,CONTRAST media ,ZINC oxide - Abstract
Purpose: Microwave imaging/sensing is an emerging technology that shows potential for healthcare diagnostic applications, particularly in breast cancer detection. This technique estimates the anatomically variant dielectric properties of the breast. Similar to other imaging modalities, nanoparticles (NPs) could potentially be utilized as contrast agents to increase contrast between healthy and malignant tissues. Methods: In this study, aqueous suspensions of NPs such as surface‐modified single‐walled carbon nanotubes, zinc oxide, and silicon dioxide are studied to assess their potential effective contrast for microwave imaging. Morphology characterization of the NPs has been achieved using atomic force microscopy (AFM) and scanning electron microscopy (SEM). The size and stability of colloidal dispersions have been characterized by dynamic light scattering technique (DLS) and Ultraviolet‐visible spectrophotometry (UV‐Vis). The dielectric characterization of the aqueous‐based colloidal suspensions is recorded over the microwave frequency range between 1 and 4 GHz. Results: Zinc oxide NP dispersion has shown an increase in the dielectric constant compared to the background medium. Furthermore, PEGylation of ZnO NPs can achieve a valid increase in the dielectric constant compared to water, which was shown to be concentration dependent. Conclusion: These results suggest that ZnO nanomaterials have the potential to be used in biomedical applications such as breast imaging to improve diagnostic capabilities. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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18. Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome.
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Tunstall, Oliver, Bhatnagar, Neha, James, Beki, Norton, Alice, O'Marcaigh, Aengus S., Watts, Tim, Greenough, Anne, Vyas, Paresh, Roberts, Irene, Wright, Michael, and the British Society for Haematology
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DOWN syndrome ,LEUKEMIA ,GUIDELINES ,GENETIC mutation ,SYNDROMES - Abstract
The article presents a guideline aimed at providing health care professionals with guidance on management of patients suffering from Transient Leukaemia of Down Syndrome(TL-DS). TL-DS may appear with overt clinical symptoms but some cases are only confirmed as a result of testing of the blood film or through GATA1 mutation evaluation.
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- 2018
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19. Experience of providing cultural safety in mental health to Aboriginal patients: A grounded theory study.
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McGough, Shirley, Wynaden, Dianne, and Wright, Michael
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CULTURE ,EMOTIONS ,GROUNDED theory ,INTELLECT ,INTERVIEWING ,RESEARCH methodology ,MENTAL health services ,NURSES ,PSYCHOLOGISTS ,STATISTICAL sampling ,TRANSCULTURAL medical care ,JUDGMENT sampling ,DATA analysis ,CULTURAL identity ,SELF-consciousness (Awareness) ,DIARY (Literary form) ,MEDICAL coding - Abstract
Abstract: The need for mental health clinicians to practice cultural safety is vital in ensuring meaningful care and in moving towards improving the mental health outcomes for Aboriginal people. The concept of cultural safety is particularly relevant to mental health professionals as it seeks to promote cultural integrity and the promotion of social justice, equity and respect. A substantive theory that explained the experience of providing cultural safety in mental health care to Aboriginal patients was developed using grounded theory methodology. Mental health professionals engaged in a social psychological process, called
seeking solutions by navigating the labyrinth to overcome the experience ofbeing unprepared . During this process participants moved from a state ofbeing unprepared to one where they began to navigate the pathway of cultural safety. The findings of this research suggest health professionals have a limited understanding of the concept of cultural safety. The experience of providing cultural safety has not been adequately addressed by organizations, health services, governments, educational providers and policy makers. Health services, organizations and government agencies must work with Aboriginal people to progress strategies that inform and empower staff to practice cultural safety. [ABSTRACT FROM AUTHOR]- Published
- 2018
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20. Enzyme reversal to explore the function of yeast E3 ubiquitin-ligases.
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MacDonald, Chris, Winistorfer, Stanley, Pope, Robert M., Wright, Michael E., and Piper, Robert C.
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UBIQUITIN ,EDIBLE fungi ,ENZYMES ,LIGASES ,YEAST - Abstract
The covalent attachment of ubiquitin onto proteins can elicit a variety of downstream consequences. Attachment is mediated by a large array of E3 ubiquitin ligases, each thought be subject to regulatory control and to have a specific repertoire of substrates. Assessing the biological roles of ligases, and in particular, identifying their biologically relevant substrates has been a persistent yet challenging question. In this study, we describe tools that may help achieve both of these goals. We describe a strategy whereby the activity of a ubiquitin ligase has been enzymatically reversed, accomplished by fusing it to a catalytic domain of an exogenous deubiquitinating enzyme. We present a library of 72 'anti-ligases' that appear to work in a dominant-negative fashion to stabilize their cognate substrates against ubiquitin-dependent proteasomal and lysosomal degradation. We then used the ligase-deubiquitinating enzyme ( DUb) library to screen for E3 ligases involved in post-Golgi/endosomal trafficking. We identify ligases previously implicated in these pathways (Rsp5 and Tul1), in addition to ligases previously localized to endosomes (Pib1 and Vps8). We also document an optimized workflow for isolating and analyzing the 'ubiquitome' of yeast, which can be used with mass spectrometry to identify substrates perturbed by expression of particular ligase- DUb fusions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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21. Isolating RNA from precursor and mature melanocytes from human vitiligo and normal skin using laser capture microdissection.
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Goldstein, Nathaniel B., Koster, Maranke I., Hoaglin, Laura G., Wright, Michael J., Robinson, Steven E., Robinson, William A., Roop, Dennis R., Norris, David A., and Birlea, Stanca A.
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NUCLEIC acids ,TYRP1 gene ,BODY covering (Anatomy) ,VITILIGO ,MICRODISSECTION - Abstract
To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes ( KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes ( SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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22. Cerebral mechanisms underlying the effects of music during a fatiguing isometric ankle-dorsiflexion task.
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Bigliassi, Marcelo, Karageorghis, Costas I., Nowicky, Alexander V., Orgs, Guido, and Wright, Michael J.
- Subjects
ISOMETRIC exercise ,DORSIFLEXION ,ATTENTION ,MUSCLE fatigue ,PSYCHOBIOLOGY ,BRAIN stimulation ,PSYCHOLOGY - Abstract
The brain mechanisms by which music-related interventions ameliorate fatigue-related symptoms during the execution of fatiguing motor tasks are hitherto under-researched. The objective of the present study was to investigate the effects of music on brain electrical activity and psychophysiological measures during the execution of an isometric fatiguing ankle-dorsiflexion task performed until the point of volitional exhaustion. Nineteen healthy participants performed two fatigue tests at 40% of maximal voluntary contraction while listening to music or in silence. Electrical activity in the brain was assessed by use of a 64-channel EEG. The results indicated that music downregulated theta waves in the frontal, central, and parietal regions of the brain during exercise. Music also induced a partial attentional switching from associative thoughts to task-unrelated factors (dissociative thoughts) during exercise, which led to improvements in task performance. Moreover, participants experienced a more positive affective state while performing the isometric task under the influence of music. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
23. The relationship between Monte Carlo estimators of heterogeneity and error for daily to monthly time steps in a small Minnesota precipitation gauge network.
- Author
-
Wright, Michael, Ferreira, Celso, Houck, Mark, and Giovannettone, Jason
- Subjects
MONTE Carlo method ,ESTIMATION theory ,METEOROLOGICAL precipitation ,QUANTILES ,SAMPLING errors ,SKEWNESS (Probability theory) ,PRECIPITATION gauges - Abstract
Precipitation quantile estimates are used in engineering, agriculture, and a variety of other disciplines. Index flood regional frequency methods pool normalized gauge data in the case of homogeneity among the constituent gauges of the region. Unitless regional quantile estimates are outputted and rescaled at each gauge. Because violation of the homogeneity hypothesis is a major component of quantile estimation error in regional frequency analysis, heterogeneity estimators should be 'reasonable proxies' of the error of quantile estimation. In this study, three Monte Carlo heterogeneity statistics tested in Hosking and Wallis (1997) are plotted against Monte Carlo estimates of quantile error for all five-or-more-gauge regionalizations in a 12 gauge network in the Twin Cities region of Minnesota. Upper-tail quantiles with nonexceedance probabilities of 0.75 and above are examined at time steps ranging from daily to monthly. A linear relationship between heterogeneity and error estimates is found and quantified using Pearson's r score. Two of Hosking and Wallis's (1997) heterogeneity measures, incorporating the coefficient of variation in one case and additionally the skewness in the other, are found to be reasonable proxies for quantile error at the L-moment ratio values characterizing these data. This result, in addition to confirming the utility of a commonly used coefficient of variation-based heterogeneity statistic, provides evidence for the utility of a heterogeneity measure that incorporates skewness information. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
24. Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS-FREM complex disorders.
- Author
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Schanze, Denny, Harakalova, Magdalena, Stevens, Cathy A., Brancati, Francesco, Dallapiccola, Bruno, Farndon, Peter, Ferraz, Victor E. F., McDonald‐McGinn, Donna M., Zackai, Elaine H., Wright, Michael, van Lieshout, Stef, Vogel, Maartje J., van Haelst, Mieke M., and Zenker, Martin
- Abstract
ABSTRACT Ablepharon macrostomia syndrome (AMS; OMIM 200110) is an extremely rare congenital malformation syndrome. It overlaps clinically with Fraser syndrome (FS; OMIM 219000), which is known to be caused by mutations in either FRAS1, FREM2, or GRIP1, encoding components of a protein complex that plays a role in epidermal-dermal interactions during morphogenetic processes. We explored the hypothesis that AMS might be either allelic to FS or caused by mutations in other genes encoding known FRAS1 interacting partners. No mutation in either of these genes was found in a cohort of 11 patients with AMS from 10 unrelated families. These findings demonstrate that AMS is genetically distinct from FS. It is proposed that it constitutes a separate entity within the group of FRAS-FREM complex disorders. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
25. ERP to chess stimuli reveal expert-novice differences in the amplitudes of N2 and P3 components.
- Author
-
Wright, Michael J., Gobet, Fernand, Chassy, Philippe, and Ramchandani, Payal Nanik
- Subjects
- *
INDIVIDUAL differences , *DIFFERENTIAL psychology , *COGNITION , *EVOKED potentials (Electrophysiology) , *ELECTROENCEPHALOGRAPHY - Abstract
ERP experiments were conducted to analyze the underlying neural events when chess players make simple judgments of a board position. Fourteen expert players and 14 age-matched novices viewed, for each of four tasks, 128 unique positions on a mini (4 × 4) chess board each presented for 0.5 s. The tasks were to respond: (a) if white king was in check, (b) if black knight was present, (c) if white king was not in check, and (d) if no black knight was present. Experts showed an enhanced N2 with check targets and a larger P3 with knight targets, relative to novices. Expert-novice differences in posterior N2 began as early as 240 ms on check-related searches. Results were consistent with the view that prolonged N2 components reflect matching of current perceptual input to memory, and thus are sensitive to experts' superior pattern recognition and memory retrieval of chunks. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
26. Introducing general practice enrolment in Australia: the devil is in the detail.
- Author
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Wright, Michael and Versteeg, Roald
- Abstract
Two recent policy updates suggest that general practice enrolment may occur in Australia in the near term. Keywords: General practice; Payment system; Health policy EN General practice Payment system Health policy 159 159 1 02/22/22 20220215 NES 220215 B I In reply: i b We thank Bailie and colleagues1 for highlighting the experiences of enrolling Indigenous Australians as part of the Practice Incentives Program - Indigenous Health Incentive (PIP-IHI) initiative. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
27. Multiple catalytic activities of Escherichia coli lysyl-t RNA synthetase ( Lys U) are dissected by site-directed mutagenesis.
- Author
-
Chen, Xiaolong, Boonyalai, Nonlawat, Lau, Catherine, Thipayang, Salinthip, Xu, Yuhong, Wright, Michael, and Miller, Andrew D.
- Subjects
ENZYME kinetics ,ESCHERICHIA coli ,CATALYSIS ,LYSYL-tRNA synthetase ,MUTAGENESIS ,ISOTHERMAL titration calorimetry ,PHOSPHATES ,KINASES - Abstract
The heat-inducible lysyl-tRNA synthetase from Escherichia coli (LysU; EC6/1/1/6.html) converts ATP to diadenosine tri- and tetraphosphates (Ap
3 A/Ap4 A) in the presence of l-lysine/Mg2+ /Zn2+ . To understand LysU in more detail, 26 mutants were prepared: six of E264, four of R269 and sixteen mutants by alanine-scanning of the inner shell/motif 2 loop. In the presence of glycerol and absence of exogenously added Zn2+ / l-lysine, we unexpectedly found that E264K catalysed the production of glycerol-3-phosphate, powered by ATP turnover to ADP. E264Q and E264N are also capable of this activity, but all three show little formation of Ap4 A/Ap3 A under normal conditions (additional Zn2+ / l-lysine/Mg2+ ). By contrast, wild-type LysU has a weaker glycerol kinase-like capability in the absence of Zn2+ and is dominated by Ap4 A/Ap3 A synthesis in its presence. Kinetic and isothermal titration calorimetry results suggest that E264 is a crucial residue for Zn2+ promotion of Ap4 A/Ap3 A synthesis. This is consistent with the hypothesis that E264 provides an anchor point for a Zn2+ ion complexed to the active site, with simultaneous coordination to the enzyme bound lysyl-adenylate intermediate and secondary substrate ATP/ADP. The glycerol kinase-like activity is uncovered on disruption of this specific coordination. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
28. Derivatization of carboxyl-terminated polybutadiene for determining relative functionality distribution.
- Author
-
Straessler, Nicholas A., Li, Ping, Parry, Shawn A., Coleman, David W., Killpack, Michael O., and Wright, Michael E.
- Subjects
POLYBUTADIENE ,CARBOXYLIC acids ,ESTERIFICATION ,GEL permeation chromatography ,CHLORIDES - Abstract
A new and highly efficient method for determining relative carboxyl group distribution in carboxyl-terminated polybutadiene has been developed using practical synthetic and analytical techniques. Using oxalyl chloride, samples of carboxyl-terminated polybutadiene were rapidly transformed to acid chlorides that were then chemically derivatized with benzyl alcohol, 4-nitrobenzyl alcohol, and 3,5-dinitrobenzyl alcohol. This provided quick and quantitative conversion to the corresponding benzyl ester derivatives. Each new derivative was fully characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. The benzyl ester modified polymers were investigated in detail to determine their relative carboxyl group concentrations. To do this, gel permeation chromatography combined with ultra violet/refractive index dual detection was employed. The 4-nitrobenzyl ester, having the highest extinction factor at 270 nm provided the best UV data for analysis. The ultra violet/refractive index data of four separate polymer samples were plotted as a function of molecular weight. The data were compared with a theoretical plot (carboxyl group = two for all molecular weights) to illustrate the relative carboxyl concentration over the entire molecular weight range. Supplemental characterization of the 4-nitrobenzyl modified polymer was carried out using matrix-assisted laser desorption ionization coupled with time of flight mass spectrometry. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
29. Pediatric palliative care provision around the world: A systematic review.
- Author
-
Knapp, Caprice, Woodworth, Lindsey, Wright, Michael, Downing, Julia, Drake, Ross, Fowler-Kerry, Sue, Hain, Richard, and Marston, Joan
- Published
- 2011
- Full Text
- View/download PDF
30. Factors Controlling the Regional Distribution of Vanadium in Groundwater.
- Author
-
Wright, Michael T. and Belitz, Kenneth
- Subjects
- *
GROUNDWATER , *VANADIUM , *CONTAMINATION of drinking water , *ANALYTICAL geochemistry , *ADSORPTION (Chemistry) - Abstract
Although the ingestion of vanadium (V) in drinking water may have possible adverse health effects, there have been relatively few studies of V in groundwater. Given the importance of groundwater as a source of drinking water in many areas of the world, this study examines the potential sources and geochemical processes that control the distribution of V in groundwater on a regional scale. Potential sources of V to groundwater include dissolution of V rich rocks, and waste streams from industrial processes. Geochemical processes such as adsorption/desorption, precipitation/dissolution, and chemical transformations control V concentrations in groundwater. Based on thermodynamic data and laboratory studies, V concentrations are expected to be highest in samples collected from oxic and alkaline groundwater. However, the extent to which thermodynamic data and laboratory results apply to the actual distribution of V in groundwater is not well understood. More than 8400 groundwater samples collected in California were used in this study. Of these samples, high (≥50 µg/L) and moderate (25 to 49 µg/L) V concentrations were most frequently detected in regions where both source rock and favorable geochemical conditions occurred. The distribution of V concentrations in groundwater samples suggests that significant sources of V are mafic and andesitic rock. Anthropogenic activities do not appear to be a significant contributor of V to groundwater in this study. High V concentrations in groundwater samples analyzed in this study were almost always associated with oxic and alkaline groundwater conditions, which is consistent with predictions based on thermodynamic data. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
31. Is there value in the Relative Value Study? Caution before Australian Medicare reform.
- Author
-
Wright, Michael
- Abstract
The federal government has announced formation of a Medicare Benefits Schedule (MBS) Review Taskforce, described as the most comprehensive review of the MBS in its near 50-year history. The Relative Value Study (RVS) was the last major collaborative attempt between the government and the medical profession to restructure the MBS. The RVS was a review of services and fees of the MBS conducted between 1994 and 2001 that was never implemented. This article provides a historical narrative of the RVS and discusses the failure of its implementation in terms of health policy theory. Understanding the specific difficulties of the RVS methodology, and the broader challenges of health care reform, may allow for more successful implementation of the current Medicare review. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
32. The duality of LysU, a catalyst for both Ap4A and Ap3A formation.
- Author
-
Wright, Michael, Boonyalai, Nonlawat, Tanner, Julian A., Hindley, Alison D., and Miller, Andrew D.
- Subjects
- *
DINUCLEOSIDE polyphosphates , *HEAT shock proteins , *ESCHERICHIA coli , *ADENOSINES , *PHOSPHATES , *EUKARYOTIC cells - Abstract
Heat shock inducible lysyl-tRNA synthetase of Escherichia coli (LysU) is known to be a highly efficient diadenosine 5′,5′′′- P1, P4-tetraphosphate (Ap4A) synthase. However, we use an ion-exchange HPLC technique to demonstrate that active LysU mixtures actually have a dual catalytic activity, initially producing Ap4A from ATP, before converting that tetraphosphate to a triphosphate. LysU appears to be an effective diadenosine 5′,5′′′- P1, P3-triphosphate (Ap3A) synthase. Mechanistic investigations reveal that Ap3A formation requires: (a) that the second step of Ap4A formation is slightly reversible, thereby leading to a modest reappearance of adenylate intermediate; and (b) that phosphate is present to trap the intermediate (either as inorganic phosphate, as added ADP, or as ADP generated in situ from inorganic phosphate). Ap3A forms readily from Ap4A in the presence of such phosphate-based adenylate traps (via a ‘reverse-trap’ mechanism). LysU is also clearly demonstrated to exist in a phosphorylated state that is more physically robust as a catalyst of Ap4A formation than the nonphosphorylated state. However, phosphorylated LysU shows only marginally improved catalytic efficiency. We note that Ap3A effects have barely been studied in prokaryotic organisms. By contrast, there is a body of literature that describes Ap3A and Ap4A having substantially different functions in eukaryotic cells. Our data suggest that Ap3A and Ap4A biosynthesis could be linked together through a single prokaryotic dual ‘synthase’ enzyme. Therefore, in our view there is a need for new research into the effects and impact of Ap3A alone and the intracellular [Ap3A]/[Ap4A] ratio on prokaryotic organisms. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
33. Mapping the Conservation Landscape.
- Author
-
Redford, Kent H., Coppolillo, Peter, Sanderson, Eric W., Da Fonseca, Gustavo A. B., Dinerstein, Eric, Groves, Craig, Mace, Georgina, Maginnis, Stewart, Mittermeier, Russell A., Noss, Reed, Olson, David, Robinson, John G., Vedder, Amy, and Wright, Michael
- Subjects
BIODIVERSITY conservation ,CONSERVATIONISTS - Abstract
Copyright of Conservation Biology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2003
- Full Text
- View/download PDF
34. Introducing general practice enrolment in Australia: the devil is in the detail.
- Author
-
Wright, Michael and Versteeg, Roald
- Abstract
The intention of enrolment is to identify and strengthen GP-patient links, and provide a mechanism supporting the delivery of evidence-based and high quality patient services that are not appropriately supported under the current health system. Although most Australians identify a usual GP, multiple practice attendance is common,3 and it can be unclear to GPs whether patients view them as their preferred doctor. In this article, we outline Australian and international experience with enrolment and suggest ways for Australia to introduce a system that benefits patients, health system funders and providers of comprehensive holistic general practice care. Keywords: General practice; Payment system; Health policy EN General practice Payment system Health policy 400 400 1 05/19/21 20210515 NES 210515 Enrolment may strengthen the link between patients and their preferred primary care providers and needs to support flexible provision of high quality care In the 2019-20 federal budget, $448 million was allocated to introduce a system of voluntary general practice enrolment for Indigenous people over 50 years of age and all Australians over 70 years of age from July 2020.1 Enrolment, also known as nomination or empanelment, allows patients to register with a specified general practitioner at their preferred general practice. [Extracted from the article]
- Published
- 2021
- Full Text
- View/download PDF
35. Cervical tracheoesophageal fistula.
- Author
-
Green, Robert P., Biller, Hugh F., Sicular, Arthur, Wright, Michael, Green, R P, Biller, H F, Sicular, A, and Wright, M
- Abstract
Four unusual cases of cervical tracheoesophageal fistula (TEF) are presented. The incidence, diagnosis and treatment of cervical TEF are discussed. Surgically, if the location is above the level of T2 a cervical approach may be utilized. The cases included a cervical "H" type TEF occurring in an adult. Congenital "H" type TEFs frequently occur in the neck. An adult presenting with a cervical "H" type TEF, having as an infant undergone repair of a thoracic TEF, is unique. Two layer closure of both trachea and esophagus with strap muscle interposition is preferred. The other cases include a TEF secondary to metastatic breast carcinoma, one associated with a stomal recurrence, and an acquired TEF following laryngectomy. Metastatic breast carcinoma resulting in a TEF is reported for the first time. Malignant TEF's are usually secondary to carcinoma of the esophagus, lung, or thyroid. Best palliation is achieved either by esophageal intubation, by colon bypass, or by gastric pull-up with esophageal exclusion. Stomal recurrence with TEF following laryngectomy is treated with one-stage resection and reconstruction with a pectoralis major myocutaneous flap and gastric pull-up. A patient 5 years post-laryngectomy illustrates an acquired non-malignant cervical TEF, a category which includes fistulas due to trauma, tracheotomy, or endotracheal tubes, instrumentation, and inflammatory disease. Prompt surgical closure as in congenital cases is the treatment of choice although select cases require medical therapy. [ABSTRACT FROM AUTHOR]
- Published
- 1983
- Full Text
- View/download PDF
36. A preliminary study of poly( p-phenylene) based nonlinear optical materials.
- Author
-
Wright, Michael E., Toplikar, Edward G., Lackritz, Hilary S., and Subrahmanyan, Suchitra
- Published
- 1995
- Full Text
- View/download PDF
37. Measuring Corporate Environmental Performance: The ICI Environmental Burden System.
- Author
-
Wright, Michael, Allen, David, Clift, Roland, and Sas, Hein
- Published
- 1997
- Full Text
- View/download PDF
38. Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1.
- Author
-
Graves, Jonathan D., Gotoh, Yukiko, Draves, Kevin E., Ambrose, Diane, Han, David K. M., Wright, Michael, Chernoff, Jonathan, Clark, Edward A., and Krebs, Edwin G.
- Subjects
ACTIN ,PROTEIN genetics ,APOPTOSIS ,GLUCOSIDASES ,GUANOSINE triphosphatase ,GTPASE-activating protein ,CYSTEINE proteinases - Abstract
Mst1 is a ubiquitously expressed serinethreonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspasemediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspasemediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinasedead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. Our findings suggest the existence of a positive feedback loop involving Mst1, and possibly the SAPK and p38 MAPK pathways, which serves to amplify the apoptotic response. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
39. NEW SOUTH WALES RURAL WATER SUPPLY: A CASE STUDY IN THE EVOLUTION OF A PROPERTY RIGHTS SYSTEM IN NATURAL RESOURCES.
- Author
-
STURGESS, GARY L. and WRIGHT, MICHAEL
- Published
- 1990
- Full Text
- View/download PDF
40. Consent forms - a necessary evil.
- Author
-
Wright, Michael
- Abstract
IN these excessively litigious times, it is prudent to be sure that an owner has consented to any procedure that is performed on their animal. The process of obtaining consent also serves to confirm that there are no misunderstandings between veterinary surgeon and client and that the client wants the particular procedure to be performed. [ABSTRACT FROM PUBLISHER]
- Published
- 1995
- Full Text
- View/download PDF
41. Management Buyouts and Industrial Relations.
- Author
-
COYNE, JOHN and WRIGHT, MICHAEL
- Abstract
Acquisition by managers of the control of firms in difficulty is taming the unions. Norman Tebbit should devise means of inducing the large public sector unions to buy the nationalised industries. [ABSTRACT FROM AUTHOR]
- Published
- 1982
- Full Text
- View/download PDF
42. Nationalised Industries: Sale of the Century?
- Author
-
CHIPLIN, BRIAN and WRIGHT, MICHAEL
- Published
- 1981
- Full Text
- View/download PDF
43. Synthesis of Novel Fluorescent-Labeled Dinucleoside Polyphosphates.
- Author
-
Wright, Michael and Miller, Andrew D.
- Published
- 2004
- Full Text
- View/download PDF
44. Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.
- Author
-
Hardcastle A, Berry AM, Campbell IM, Zhao X, Liu P, Gerard AE, Rosenfeld JA, Sisoudiya SD, Hernandez-Garcia A, Loddo S, Di Tommaso S, Novelli A, Dentici ML, Capolino R, Digilio MC, Graziani L, Rustad CF, Neas K, Ferrero GB, Brusco A, Di Gregorio E, Wellesley D, Beneteau C, Joubert M, Van Den Bogaert K, Boogaerts A, McMullan DJ, Dean J, Giuffrida MG, Bernardini L, Varghese V, Shannon NL, Harrison RE, Lam WWK, McKee S, Turnpenny PD, Cole T, Morton J, Eason J, Jones MC, Hall R, Wright M, Horridge K, Shaw CA, Chung WK, and Scott DA
- Subjects
- Animals, DNA Copy Number Variations, Diaphragm, Mice, Hernias, Diaphragmatic, Congenital genetics
- Abstract
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
45. Further delineation of phenotypic spectrum of SCN2A-related disorder.
- Author
-
Richardson R, Baralle D, Bennett C, Briggs T, Bijlsma EK, Clayton-Smith J, Constantinou P, Foulds N, Jarvis J, Jewell R, Johnson DS, McEntagart M, Parker MJ, Radley JA, Robertson L, Ruivenkamp C, Rutten JW, Tellez J, Turnpenny PD, Wilson V, Wright M, and Balasubramanian M
- Subjects
- Child, Female, Humans, Male, NAV1.2 Voltage-Gated Sodium Channel genetics, Phenotype, Seizures genetics, Autism Spectrum Disorder genetics, Intellectual Disability diagnosis, Intellectual Disability genetics
- Abstract
SCN2A-related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype-genotype association in SCN2A-related disorders was further delineated by collecting detailed clinical and molecular characteristics. Using previously proposed genotype-phenotype hypotheses based on variant function and position, the potential of phenotype prediction from the variants found was examined. Patients were identified through the Deciphering Developmental Disorders study and gene matching strategies. Phenotypic information and variant interpretation evidence were collated. Seventeen previously unreported patients and five patients who had been previously reported (but with minimal phenotypic and segregation data) were included (10 males, 12 females; median age 10.5 years). All patients had developmental delays and the majority had intellectual disabilities. Seizures were reported in 15 of 22 (68.2%), four of 22 (18.2%) had autism spectrum disorder and no patients were reported with episodic ataxia. The majority of variants were de novo. One family had presumed gonadal mosaicism. The correlation of the use of sodium channel-blocking antiepileptic drugs with phenotype or genotype was variable. These data suggest that variant type and position alone can provide some predictive information about the phenotype in a proportion of cases, but more precise assessment of variant function is needed for meaningful phenotype prediction., (© 2021 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
46. Serum concentrations of estriol vary widely after application of vaginal oestriol cream.
- Author
-
Te West N, Day R, Graham G, Wright M, White C, Popovic G, and Moore KH
- Subjects
- Estradiol, Estrogens, Estrone, Female, Humans, Estriol, Vaginal Creams, Foams, and Jellies
- Abstract
Aims: The aim of this study was to establish the pharmacokinetic profile of serum oestriol (E
3 ) concentrations over 24 h following application of vaginal E3 in chronic users (>12 weeks of E3 use). The interindividual and intraindividual differences before and after E3 were examined., Methods: Ten women participated. Vaginal cream was omitted for ≥36 h prior to the study days. Blood sampling was performed for E3 , oestradiol and oestrone concentrations prior to cream application and at 1, 2, 3, 5, 8, 10, 12 and 24 h afterwards. In five women, all samples were repeated on a separate day., Results: E3 was absorbed rapidly in most women. Peak serum E3 concentration occurred around 2 h (range 1-5 h). The decline in E3 concentrations was also rapid: falling <100 pmol L-1 in six out of ten women within 8 h and returning to ≤ 10 pmol L-1 at 24 h in nine out of the ten patients. Interindividual variability for peak concentrations was considerable (mean 546 pmol L-1 ; 95% CI 349-743). Area under the concentration-time curve (AUC) values over a dosage interval also varied widely: mean 2145 pmol.h L-1 ; 95% CI 1422-3233. However, repeated measurements in the same woman were highly (peaks: ρ = 0.94) or moderately (AUC: P = 0.74) correlated., Conclusions: Postmenopausal E3 concentrations are negligible. Serum E3 concentrations of chronic users of E3 cream varied greatly; however, concentrations declined rapidly within 8 h, generally reaching 'postmenopausal' levels by 24 h. The basis for the variation between subjects needs further elucidation. Additional research is required to establish the safety of topical E3 ., (© 2020 British Pharmacological Society.)- Published
- 2021
- Full Text
- View/download PDF
47. The phenotype of Sotos syndrome in adulthood: A review of 44 individuals.
- Author
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Foster A, Zachariou A, Loveday C, Ashraf T, Blair E, Clayton-Smith J, Dorkins H, Fryer A, Gener B, Goudie D, Henderson A, Irving M, Joss S, Keeley V, Lahiri N, Lynch SA, Mansour S, McCann E, Morton J, Motton N, Murray A, Riches K, Shears D, Stark Z, Thompson E, Vogt J, Wright M, Cole T, and Tatton-Brown K
- Subjects
- Adult, Child, Facies, Female, Humans, Intellectual Disability genetics, Male, Sotos Syndrome genetics, Sotos Syndrome psychology, Phenotype, Sotos Syndrome physiopathology
- Abstract
Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
- Full Text
- View/download PDF
48. Meier-Gorlin syndrome: growth and secondary sexual development of a microcephalic primordial dwarfism disorder.
- Author
-
de Munnik SA, Otten BJ, Schoots J, Bicknell LS, Aftimos S, Al-Aama JY, van Bever Y, Bober MB, Borm GF, Clayton-Smith J, Deal CL, Edrees AY, Feingold M, Fryer A, van Hagen JM, Hennekam RC, Jansweijer MC, Johnson D, Kant SG, Opitz JM, Ramadevi AR, Reardon W, Ross A, Sarda P, Schrander-Stumpel CT, Sluiter AE, Temple IK, Terhal PA, Toutain A, Wise CA, Wright M, Skidmore DL, Samuels ME, Hoefsloot LH, Knoers NV, Brunner HG, Jackson AP, and Bongers EM
- Subjects
- Cell Cycle Proteins genetics, Child, Preschool, Cohort Studies, Congenital Microtia, Ear abnormalities, Female, Growth Disorders drug therapy, Growth Disorders genetics, Human Growth Hormone blood, Human Growth Hormone therapeutic use, Humans, Infant, Male, Micrognathism drug therapy, Micrognathism genetics, Mutation, Origin Recognition Complex genetics, Patella abnormalities, Urogenital Abnormalities, Growth Charts, Growth Disorders diagnosis, Micrognathism diagnosis, Sexual Development genetics
- Abstract
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This complex is essential for DNA replication and therefore mutations are expected to impair cell proliferation and consequently could globally reduce growth. However, detailed growth characteristics of MGS patients have not been reported, and so this is addressed here through study of 45 MGS patients, the largest cohort worldwide. Here, we report that growth velocity (length) is impaired in MGS during pregnancy and first year of life, but, thereafter, height increases in paralleled normal reference centiles, resulting in a mean adult height of -4.5 standard deviations (SD). Height is dependent on ethnic background and underlying molecular cause, with ORC1 and ORC4 mutations causing more severe short stature and microcephaly. Growth hormone therapy (n = 9) was generally ineffective, though in two patients with significantly reduced IGF1 levels, growth was substantially improved by GH treatment, with 2SD and 3.8 SD improvement in height. Growth parameters for monitoring growth in future MGS patients are provided and as well we highlight that growth is disproportionately affected in certain structures, with growth related minor genital abnormalities (42%) and mammary hypoplasia (100%) frequently present, in addition to established effects on ears and patellar growth., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
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49. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals.
- Author
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Garcia Segarra N, Mittaz L, Campos-Xavier AB, Bartels CF, Tuysuz B, Alanay Y, Cimaz R, Cormier-Daire V, Di Rocco M, Duba HC, Elcioglu NH, Forzano F, Hospach T, Kilic E, Kuemmerle-Deschner JB, Mortier G, Mrusek S, Nampoothiri S, Obersztyn E, Pauli RM, Selicorni A, Tenconi R, Unger S, Utine GE, Wright M, Zabel B, Warman ML, Superti-Furga A, and Bonafé L
- Subjects
- Adult, Alternative Splicing genetics, Arthropathy, Neurogenic ethnology, Arthropathy, Neurogenic pathology, CCN Intercellular Signaling Proteins chemistry, Calcinosis diagnostic imaging, Child, Child, Preschool, DNA, Complementary genetics, Hand diagnostic imaging, Humans, Joint Diseases congenital, Pelvis diagnostic imaging, Pelvis pathology, Polymorphism, Single Nucleotide genetics, Protein Structure, Tertiary, RNA, Messenger genetics, RNA, Messenger metabolism, Radiography, Reproducibility of Results, Spine diagnostic imaging, Spine pathology, Arthropathy, Neurogenic diagnostic imaging, Arthropathy, Neurogenic genetics, CCN Intercellular Signaling Proteins genetics, Mutation genetics
- Abstract
Progressive pseudorheumatoid dysplasia (PPRD) is a genetic, non-inflammatory arthropathy caused by recessive loss of function mutations in WISP3 (Wnt1-inducible signaling pathway protein 3; MIM 603400), encoding for a signaling protein. The disease is clinically silent at birth and in infancy. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Affected children are referred to pediatric rheumatologists and orthopedic surgeons; however, signs of inflammation are absent and anti-inflammatory treatment is of little help. Bony enlargement at the interphalangeal joints progresses leading to camptodactyly. Spine involvement develops in late childhood and adolescence leading to short trunk with thoracolumbar kyphosis. Adult height is usually below the 3rd percentile. Radiographic signs are relatively mild. Platyspondyly develops in late childhood and can be the first clue to the diagnosis. Enlargement of the phalangeal metaphyses develops subtly and is usually recognizable by 10 years. The femoral heads are large and the acetabulum forms a distinct "lip" overriding the femoral head. There is a progressive narrowing of all articular spaces as articular cartilage is lost. Medical management of PPRD remains symptomatic and relies on pain medication. Hip joint replacement surgery in early adulthood is effective in reducing pain and maintaining mobility and can be recommended. Subsequent knee joint replacement is a further option. Mutation analysis of WISP3 allowed the confirmation of the diagnosis in 63 out of 64 typical cases in our series. Intronic mutations in WISP3 leading to splicing aberrations can be detected only in cDNA from fibroblasts and therefore a skin biopsy is indicated when genomic analysis fails to reveal mutations in individuals with otherwise typical signs and symptoms. In spite of the first symptoms appearing in early childhood, the diagnosis of PPRD is most often made only in the second decade and affected children often receive unnecessary anti-inflammatory and immunosuppressive treatments. Increasing awareness of PPRD appears to be essential to allow for a timely diagnosis., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
- Full Text
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50. Dominant negative mutations in the C-propeptide of COL2A1 cause platyspondylic lethal skeletal dysplasia, torrance type, and define a novel subfamily within the type 2 collagenopathies.
- Author
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Zankl A, Neumann L, Ignatius J, Nikkels P, Schrander-Stumpel C, Mortier G, Omran H, Wright M, Hilbert K, Bonafé L, Spranger J, Zabel B, and Superti-Furga A
- Subjects
- Child, Preschool, Fatal Outcome, Female, Fetal Death, Follow-Up Studies, Foot Deformities, Congenital pathology, Hand Deformities, Congenital pathology, Humans, Infant, Infant, Newborn, Male, Osteochondrodysplasias pathology, Phenotype, Collagen Type II genetics, Musculoskeletal Abnormalities, Mutation, Osteochondrodysplasias genetics
- Abstract
Platyspondylic lethal skeletal dysplasia (PLSD) Torrance type (PLSD-T) is a rare skeletal dysplasia characterized by platyspondyly, brachydactyly, and metaphyseal changes. Generally a perinatally lethal disease, a few long-term survivors have been reported. Recently, mutations in the carboxy-propeptide of type II collagen have been identified in two patients with PLSD-T, indicating that PLSD-T is a type 2 collagen-associated disorder. We studied eight additional cases of PLSD-T and found that all had mutations in the C-propeptide domain of COL2A1. The mutational spectrum includes missense, stop codon and frameshift mutations. All non-sense mutations were located in the last exon, where they would escape non-sense-mediated RNA-decay. We conclude that PLSD-T is caused by mutations in the C-propeptide domain of COL2A1, which lead to biosynthesis of an altered collagen chain (as opposed to a null allele). Similar mutations have recently been found to be the cause of spondyloperipheral dysplasia, a non-lethal dominant disorder whose clinical and radiographical features overlap those of the rare long-term survivors with PLSD-T. Thus, spondyloperipheral dysplasia and PLSD-T constitute a novel subfamily within the type II collagenopathies, associated with specific mutations in the C-propeptide domain and characterized by distinctive radiological features including metaphyseal changes and brachydactyly that set them apart from other type 2 collagenopathies associated with mutations in the triple-helical domain of COL2A1. The specific phenotype of C-propeptide mutations could result from a combination of diminished collagen fibril formation, toxic effects through the accumulation of unfolded collagen chains inside the chondrocytes, and alteration of a putative signaling function of the carboxy-propeptide of type 2 collagen., ((c) 2005 Wiley-Liss, Inc.)
- Published
- 2005
- Full Text
- View/download PDF
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