162 results on '"Whelan L"'
Search Results
2. Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients
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Whelan, L., Dockery, A., Stephenson, K.A.J., Zhu, Julia, Kopčić, E., Post, I.J.M., Khan, M., Corradi, Z., Wynne, N., O' Byrne, J.J., Duignan, E., Silvestri, Giuliana, Roosing, S., Cremers, F.P.M., Keegan, D.J., Kenna, P.F., and Farrar, G.J.
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All institutes and research themes of the Radboud University Medical Center ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] - Abstract
Contains fulltext : 293457.pdf (Publisher’s version ) (Open Access) Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.
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- 2023
3. Identification of Presurgical Risk Factors for the Development of Chronic Postsurgical Pain in Adults: A Comprehensive Umbrella Review
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Sydora BC, Whelan LJ, Abelseth B, Brar G, Idris S, Zhao R, Leonard AJ, Rosenbloom BN, Clarke H, Katz J, Beesoon S, and Rasic N
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chronic postsurgical pain ,risk factors ,predictors ,umbrella review ,surgery ,Medicine (General) ,R5-920 - Abstract
Beate C Sydora,1 Lindsay Jane Whelan,1,2 Benjamin Abelseth,2 Gurpreet Brar,3 Sumera Idris,3 Rachel Zhao,4 Ashley Jane Leonard,4 Brittany N Rosenbloom,5 Hance Clarke,6 Joel Katz,6,7 Sanjay Beesoon,1 Nivez Rasic2,8 1Department of Surgery Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada; 2Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; 3Health Systems Knowledge and Evaluation, Alberta Health Services, Edmonton, AB, Canada; 4Knowledge Resource Service, Alberta Health Services, Edmonton, AB, Canada; 5Toronto Academic Pain Medicine Institute, Toronto, ON, Canada; 6Department of Anesthesia and Pain Management, Toronto General Hospital, UHN, Toronto, ON, Canada; 7Department of Psychology, York University, Toronto, ON, Canada; 8Department of Anesthesiology, Perioperative & Pain Medicine, University of Calgary, Calgary, AB, CanadaCorrespondence: Nivez Rasic, Department of Anesthesiology, Perioperative and Pain Medicine, University of Calgary, Medical Lead, Vi Riddell Pain & Rehabilitation Program, Acute Pain Lead, Alberta Pain Strategy, Alberta Children’s Hospital, 28 Oki Drive NW, Calgary, AB, T3B 6A8, Canada, Tel +403-955-7810, Email Nivez.Rasic@albertahealthservices.ca Sanjay Beesoon, Assistant Scientific Director, Surgery Strategic Clinical Network, Alberta Health Services, 02-048 South Tower, Seventh Street Plaza, 10030 107 St NW, Edmonton, AB, T5J 3E4, Canada, Tel +780-735-1682 ; +780-218-4786, Email Sanjay.Beesoon@albertahealthservices.caPurpose: Risk factors for the development of chronic postsurgical pain (CPSP) have been reported in primary studies and an increasing number of reviews. The objective of this umbrella review was to compile and understand the published presurgical risk factors associated with the development of CPSP for various surgery types.Methods: Six databases were searched from January 2000 to June 2023 to identify meta-analyses, scoping studies, and systematic reviews investigating presurgical CPSP predictors in adult patients. Articles were screened by title/abstract and subsequently by full text by two independent reviewers. The selected papers were appraised for their scientific quality and validity. Data were extracted and descriptively analyzed.Results: Of the 2344 retrieved articles, 36 reviews were selected for in-depth scrutiny. The number of primary studies in these reviews ranged from 4 to 317. The surgery types assessed were arthroplasty (n = 13), spine surgery (n = 8), breast surgery (n = 4), shoulder surgery (n = 2), thoracic surgery (n = 2), and carpal tunnel syndrome (n = 1). One review included a range of orthopedic surgeries; six reviews included a variety of surgeries. A total of 39 presurgical risk factors were identified, some of which shared the same defining tool. Risk factors were themed into six broad categories: psychological, pain-related, health-related, social/lifestyle-related, demographic, and genetic. The strength of evidence for risk factors was inconsistent across different reviews and, in some cases, conflicting. A consistently high level of evidence was found for preoperative pain, depression, anxiety, and pain catastrophizing.Conclusion: This umbrella review identified a large number of presurgical risk factors which have been suggested to be associated with the development of CPSP after various surgeries. The identification of presurgical risk factors is crucial for the development of screening tools to predict CPSP. Our findings will aid in designing screening tools to better identify patients at risk of developing CPSP and inform strategies for prevention and treatment.Plain Language Summary: Chronic postsurgical pain (CPSP) is pain experienced predominantly at the surgical site for longer than 3 months after a surgical procedure. Depending on surgery type, it can affect between 10 and 80% of people undergoing major surgeries, which may have negative effects such as a lower quality of life, disability, and persistent opioid use. Targeted identification and management of at risk patients in the presurgical phase may decrease the risk of CPSP. This umbrella review generated a list of potential risk factors for CPSP from evidence-based reviews of the current literature.Thirty-nine presurgical risk factors were identified in this review. Risk factors are divided into six broad categories: psychological, pain-related, health-related, demographic, genetic, and social/lifestyle-related. Although the strength of evidence for individual risk factors varied across reviews, risk factors in the psychological category consistently showed a strong impact on the development of CPSP.It is vital to understand which individuals are vulnerable and at risk for CPSP. The findings of this umbrella review will aid in designing screening tools to identify surgical candidates at risk. Some risk factors, such as genetics, cannot be altered. However, many identified risk factors are modifiable and may inform strategies for the prevention and treatment of CPSP using screening tools. Our findings may guide future research to consider an in-depth analysis of risk factor characterization to group modifiable presurgical risk factors. At risk patients will be offered psychological, physical, and pharmacological treatments accordingly to mitigate their risk of developing CPSP and ultimately improve patient outcomes in surgery.Keywords: chronic postsurgical pain, risk factors, predictors, umbrella review, surgery
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- 2024
4. Brachypodium distachyon Cell Suspension Cultures: Establishment and Utilisation
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Hunt, D., Chambers, J.P., Behpouri, A., Kelly, S.P., Whelan, L., Pietrzykowska, M., Downey, F., Mccabe, P.F., and Ng, C.K.-Y.
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- 2014
5. OP02. Interrogating and correcting fine‐scale genetic structure in large (>36,000 samples) GWAS datasets using scalable haplotype sharing methods
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Gilbert, Edmund, O’Reilly, Seamus, Merrigan, Michael, McGettingan, Darren, Vitart, Veronique, Joshi, Peter K, Clark, David W, Campbell, Harry, Hayward, Caroline, Ring, Susan M, Golding, Jean, Goodfellow, Stephanie, Navarro, Pau, Kerr, Shona M, Amador, Carmen, Campbell, Archie, Haley, Chris S, Porteous, David J, Cavalleri, Gianpiero L, Wilson, James F, Byrne, RP, van Rheenen, W, Veldink, JH, McLaughlin, RL, Fitzgerald, Joan, Fahey, Laura, Whitton, Laura, Donohoe, Gary, Morris, Derek W, Smyth, LJ, Wooster, C, Kilner, J, Kee, F, Young, I, McGuinness, B, Maxwell, AP, McKay, GJ, McKnight, AJ, Maloney, DM, Chadderton, N, Millington-Ward, S, Farrar, GJ, Lambert, DM, Nguengang-Wakap, S, Olry, A, Rath, A, Murphy, D, Lynch, SA, Treacy, EP, Gunne, E, McGarvey, C, Hamilton, K, Savage, S, Rasheed, E, Rashid, A, Keogh, E, MacNamara, B, Collison, C, Brazil, N, Whatley, S, Crowley, VEF, Murphy, DN, Turner, J, Doyle, Samantha, Abidin, Zaza, Senanayake, Suranga, James, Stephanie, Yap, Mei, Hart, Caroline, Crushell, Ellen, Smyth, Shane, Green, Andrew, Treacy, Eileen, Lynch, Tim, Pastores, Gregory, Laffan, Aoife, O’Byrne, James, Palfi, A, Yesmambetov, A, Ormond, CM, Ryan, NM, Heron, EA, Gill, M, Corvin, AP, Kelly, CM, Doherty, MA, Hengeveld, JC, Campbell, C, Leu, C, Delanty, N, Lal, D, Cavalleri, GL, Angel, CZ, McNally, CJ, McKenna, DJ, Breslin, EM, Cassidy, LM, Martiniano, R, Mattiangeli, V, Silva, AM, Bradley, DG, Kearney, H, Balagura, G, Lewis-Smith, D, Ganesan, S, Gan, J, Galer, PD, Wang, Y, Tan, NCK, Lench, NJ, Steward, CA, Krause, R, Robinson, P, Helbig, I, Finnegan, LK, Kenna, P, Carty, M, Bowie, AG, Whelan, L, Dockery, A, Kenna, PF, Keegan, D, Silvestri, G, Khan, M, Cornelis, SS, Dhaenens, CM, Humphries, P, Cremers, FPM, Roosing, S, Broin, Pilib Ó, Morris, Derek, McVeigh, Úna M, McVeigh, Terri P, Miller, Nicola, Kerin, Michael J, Flaus, Andrew, Irwin, RE, Thursby, SJ, Ondičová, M, Pentieva, K, McNulty, H, Richmond, C, Caffrey, A, Lees-Murdock, DJ, McLaughlin, M, Cassidy, T, Suderman, M, Relton, CL, Walsh, CP, Carrigan, M, Maloney, D, Hanlon, K, Bookey, N, Drago, P, Parle-McDermott, A, Flynn, PM, Toulouse, A, Bermingham, N, Jansen, M, Hand, CK, Skelly, RD, Cole, J, Berkeley, M, Dinneen, Thomas, O’Cónail, A, Kirov, George, Lopez, Lorna M, Gallagher, Louise, Ning, Z, Williams, JM, Kumari, R, Baranov, PV, Moore, T, Bhandari, Sushil, Hillman, Sara, Dolma, Padma, Mukerji, Mitali, Prasher, Bhavana, Montgomery, Hugh E., Gunne, EA, Ward, A, Treacy, E, Lambert, D, Benson, KA, Murray, S, Senum, SR, Kennedy, C, Yachnin, K, Gangadharan, N, Harris, PC, Conlon, P, Zhu, J, Wynne, N, McKenna, C, Humphreys, M, McNerlan, S, Dabir, T, Rea, G, Morrison, PJ, Donnelly, DE, Jeffers, L, Sasaki, E, Kelly, H, Hayes, B, Ryan, K, Carolan, E, Betts, D, Green, A, Sheerin, A, Grabowsky, L, James, S, Senanayake, S, Abidin, Z, O’Byrne, J, Pastores, G, McConnell, V, Bradley, L, Reid, J, Fitzsimons, D, Dempster, M, Pentony, Michaela, Bradley, Lisa, Connor, Pamela O’, Kirk, Claire W, Donnelly, Deirdre E, Hardy, Rachel, Shepherd, Charles W, Morrison, Patrick J, Doyle, S, McVeigh, T, O’Byrne, JJ, Senanayake, SL, Sadok, S, Pastores, GM, Forde, R, Rakovac, A, Abdelfadil, S, Mac Namara, B, O’Connor, P, Heggarty, S, Hart, P, Morgan, NE, Dorris, E, Cummins, E, Adeeb, F, Taylor, C, Savic, S, Killeen, O, Fraser, A, Wilson, AG, Murphy, Jane, Kirk, Claire, Prendiville, Terence, Ward, Deirdre, Galvin, Joseph, Lynch, Sally Ann, Carroll, C, Kirk, C, Murphy, J, Duff, M, Mooney, E, Clark, T, King, C, Fallah, L, and Hinde, J
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Poster Presentations ,Abstracts ,Oral Presentations - Abstract
Background Age-related cognitive decline results in increased difficulty in performing tasks that require memory or rapid information processing. Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning. The polygenetic contribution to cognitive resilience requires large data sets for analysis. In addition, longitudinal data is needed to identify individual differences in cognitive performance over time. The UK Biobank cohort of over 500,000 participants over the age of 40 offers the potential to advance research on the genetics and biology of cognitive resilience. Methods We created a longitudinal cognitive resilience phenotype by combining the phenotypic cognitive parameter of current reaction time with a proxy phenotype of education years (EY). We used this resilience phenotype, in genome-wide association studies (GWAS) to identify genes and gene sets that influence the biological pathways involved in resilience. To remove the influence of the EY on the analysis we compared genetic data on participants that displayed resilience to those that showed expected cognitive decline. Results GWAS outputs analysis showed 273 significantly enriched genes for participants that demonstrated resilience. Genotype–tissue expression was significant in brain tissue, particularly in the anterior cingulate cortex, frontal cortex, and hippocampus. Biological Pathway analysis includes synapse, post synaptic density and neuron guidance. Conclusion This analysis shows an association between cognitive resilience and enrichment of neuronal activity. Confirmatory examination of these findings in datasets with strong longitudinal cognitive data, such and the Health and Retirement Study, is ongoing., Introduction Type 1 diabetes (T1D) is a polygenic disease characterised by autoimmune inflammatory destruction of the pancreas and subsequent hyperglycaemia. Several GWAS have identified loci associated with T1D risk, but recent evidence suggests that epigenetic changes in DNA methylation may have a causal role in T1D. Methods To identify potential methylation-based biomarkers of T1D, blood-derived DNA from 250 individuals with ≥15 years duration of T1D was compared to 391 controls with no evidence of diabetes. All individuals were from the British Isles. DNA was bisulphite treated using the EZ DNA Methylation Kit (Zymo). The Infinium HD Methylation Assay MethylationEPIC BeadChips (Illumina) were used to determine the methylation status of >850,000 CpG sites, gene bodies and promoters. Results MethylationEPIC data was analysed using GenomeStudio v2011 and Partek Genomics Suite v7.0. Comparing T1D with controls identified 1,706 CpG sites with significantly different (p±2 fold change). Genes including HLA‐DRB1, HLA‐DQA1 and PLEKHA1 have been previously linked to T1D and contained >2 differently methylated CpG sites ≥p, Introduction Rare diseases (RDs) are a public health priority but their scarcity and diversity leads to a lack of knowledge and expertise. Accurate epidemiological information about RDs is necessary to inform public policy, but without an Irish rare disease registry, there is a dearth of primary data. Methods Collaborative work with Orphanet Coordination derived a global point prevalence of RDs from the ‘Orphanet Epidemiological File’ (http://www.orphadata.org) by selecting RDs described by ‘point prevalence’ from predefined geographic regions, and summing point prevalences. In the National Rare Disease Office, expert opinion and disease-specific publications were used to adapt a ‘high prevalence’ list for Ireland. Results Globally, ‘point prevalence’ describes 5,304 RDs ≥85.9%). The minimum cumulative point prevalence of RDs is 3.5‐5.9% of the population. While globally 84.5% RDs analysed ≥n=3585) had a point prevalence of 1/100,000. To construct a comparable Irish ‘high‐ prevalence’ list, 191 RDs with known prevalence >1/100,000 across all countries were drawn from the global list. A further 147 diseases with possible prevalence >1/100,000 in Ireland due to ethnic, environmental or founder‐effect are currently under consideration for inclusion. Conclusion 3.5%‐5.9% is the first evidence‐based estimate of the global population prevalence of RDs. Creation of an Irish list of high‐prevalence RDs permits development of care pathways and systems that address the needs of the majority of Irish people with RDs. Implementation of RD codification in eHealth Ireland will provide more accurate data., Introduction The acute hepatic porphyrias, including acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HP) along with familial Porphyria Cutanea Tarda (fPCT) are autosomal dominantly inherited disorders affecting key enzymes in the haem biosynthetic pathway. Clinically these disorders may manifest as photosensitive skin lesions (VP, HP and PCT) and/or acute neuropathic episodes (AIP, VP and HP). All demonstrate variable penetrance and expressivity. Thus, while biochemical investigations, including blood, urine and faecal porphyrin analysis, are critical for the diagnosis of active porphyric disease, these investigations may not be sensitive enough to identify presymptomatic variant carriers. Hence molecular genetic analysis has become an important component in kindred follow-up for identifying porphyria susceptibility. Methods The Biochemistry Department, St James’s Hospital, Dublin, has established a molecular diagnostic service based on direct nucleotide sequencing to facilitate diagnosis of genetic susceptibility to AIP, VP, HCP and PCT respectively. Results To date over 30 different genetic variants linked with a porphyria phenotype have been identified in different kindreds including non‐Irish. The spectrum of variants includes missense, nonsense, splice‐site and small insertions and deletions e.g. HMBS ≥R26C, R26H, IVS4+1G>A), PPOX ≥IVS4‐1G>A, Q435X, W427X, A150D, Q375X) and CPO ≥R332Q, R332W, c.1291‐1292 ins TG). In addition, novel variants have been identified in collaboration with Cardiff Porphyria Centre. Conclusion This unique insight into the molecular basis of porphyrias in the ROI indicates that acute porphyrias and fPCT are genetically heterogeneous. Furthermore, the variant scanning assay in St James’s Hospital has identified pathogenic variants in >93% of confirmed porphyria kindreds, Background The developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies which co-present with intellectual disability, and occur in cases without a family history of epilepsy. Their severe phenotype means that DEEs are thought to be primarily monogenic, caused by highly damaging rare mutations. Currently, analysis of exome sequence data can identify a causative mutation in around 40% of DEEs. Little is known about the genetic architecture of the remaining DEEs which screen-negative after genomic analysis. Here, we used a method known as polygenic risk scoring (PRS) to test whether the burden of common genetic variation is relevant to the development of the DEEs. Methods Exome and GWAS data on DEE cases (n=745), and population controls (n=75,000) were obtained from the DDD cohort and Ukbiobank, respectively. Damaging mutations in known epilepsy genes were bioinformatically inferred. PRS were calculated using the most recent ILAE GWAS of epilepsy and compared between i) DEE cases and the general population, and ii) DEE cases with and without damaging mutations. Results DEE cases with and without inferred damaging mutations were found to have elevated PRS for epilepsy. We did not detect a significant difference in PRS between DEE cases with and without damaging mutations. Discussion This research provides the first evidence that common genetic variation contributes to the development of the DEEs. Our results suggest common genetic variation contributes to DEE status irrespective of the presence of a highly damaging rare genetic variant. Further work in additional cohorts is required to extend these results., Rationale The phenotypic features in a person with epilepsy are often complex with regards to seizure presentations, which is acknowledged by the most recent revision of the seizure classification by the International League Against Epilepsy (ILAE). We provide updated seizure-related human phenotype ontology (HPO) terms to facilitate a deep phenotypic interpretation of heretofore unexplained genetic epilepsies. Methods The Epilepsiome project is a Task Force of the Genetics Commission of the ILAE and represent the link to the gene curation efforts within the ClinGen Epilepsy Clinical Domain Working Group (CDWG). Within the efforts to align terminology used in the diagnostic space, the Epilepsiome Project revised HPO terms for epileptic seizures. The updated classification was built through an online portal and consensus was achieved through biweekly conference calls. Results Focal, generalised and neonatal HPO seizure terminologies were constructed according to the most recent ILAE classification and aligned with the existing HPO structure. This ontology allows capture of clinical information at various levels of detail and aims to preserve the onset, awareness and motor/non-motor nature of each seizure type, using multiple parentages. We integrated other frequently observed seizures currently not included in the ILAE, which required a separate branch within the ontology due to biological peculiarity of their age of onset, their clinical significance or genetic architecture. Conclusions Improvements in HPO terms for epileptic seizures will enable a more versatile seizure ontology leading to deep phenotyping of people with epilepsy to improve associations with genomic data in both a research and diagnostic setting., Purpose Target5000 aims to genetically characterise approximately 5000 people in Ireland with an inherited retinal degeneration (IRD). Thus far, over 1,000 IRD patients have been sequenced for variants in 260 IRD genes. One arm of the project focuses on improving detection of candidate variants by whole genome sequencing (WGS), by analysing non-coding mutations and performing functional analysis. Approach IRD patients are clinically diagnosed by Target5000 ophthalmologists. When informed consent is given, the Target5000 study employs target capture next generation sequencing (NGS), with a positive candidate detection rate of 68%. To improve detection rates, whole-gene or WGS was employed on a case-dependent basis to identify pathogenic intronic variants not previously captured. Results One common form of IRD is ABCA4-associated Stargardt disease (STGD1), often caused by deep-intronic variants. Thus far, 36 ‘unresolved’ STGD1 and cone-rod dystrophy cases have undergone targeted ABCA4 whole-gene sequencing, positively identifying a candidate in ~50% of cases. A variant in intron 30 resulting in a pseudoexon inclusion was particularly frequent and found in 5/16 (likely) solved cases. Furthermore, 40 patient samples have undergone WGS. Conclusions An objective of Target5000 is to provide actionable outcomes empowering patients with genetic diagnoses and potentially future access to clinical trials or approved treatments, where appropriate. The results presented highlight the significant value of a target capture NGS strategy as a preliminary diagnostic measure, with remaining elusive cases undergoing more extensive genetic analysis. This methodology improves variant detection rates and progresses the goal of fully elucidating the genetic architecture of IRDs in Ireland., Background Copy Number Variants (CNVs) are large genomic deletions/duplications of >1kb, spanning regions that can encompass one or many genes. Though a common form of structural variation, pathogenic CNVs, of population freq., The Ladakhi people dwell in the Jammu and Kashmir regions of India, between the Karakoram and Himalayan mountain ranges, at ≥3400 meters altitude. The Ladakhi share similar linguistic, cultural and religious practices with Tibetans. However, relative to Tibetans, the Ladakhi are very poorly studied at the level of population structure and genetic selection. In this context, we set out to conduct a genomic survey of population structure in representative samples of the Ladakhi people. Methods We genotyped 310 Ladakhi DNA samples using the Illumina Global Screening Array gene chip. We merged the Ladakhi with data from 800 individuals representing different reference language groups including; Sino-Tibetan (Tibetans, Sherpa, Han), Indo-European (Indo-Aryan, Hazara), Austroasiatic (Munda) and Burusho (a linguistic isolate in Jammu-Kashmir). We performed ADMIXTURE, principal component analysis (PCA), fineSTRUCTURE and ChromoPainter analysis on the combined autosomal data. Results In PCA plots, the Ladakhi population cluster together with Sherpa and Tibetans, forming a distinct Himalayan group, different from other mainland populations of South and East Asia. ADMIXTURE analysis at k=4 suggests ancestry proportions in the Ladakhi to be approximately 50% Highlander (Tibetan/Sherpa) and 50% Indo-European. These results suggest contemporary Ladakhi people are the admixed of Tibetans and Indo-Europeans. Conclusions Our results suggests a considerable component of the Ladakhi genome descends from ancestral highlander populations residing on the Tibetan plateau for the last 35,000 years, with subsequent admixture with neighbouring Indo-European populations., Background The EU recognises rare disease (RD) as life threatening with delays in establishing a diagnosis and treatment. The Irish National Plan for RDs (2014) recommended epidemiological studies of RD prevalence to improve both cost efficiencies and care of patients with RD’s. Objective To derive the incidence of paediatric RD and the number of paediatric RD mortality cases through analysis of records held at two major tertiary paediatric hospitals, for children born in the year 2000. Methods Cases were identified using electronic/manual records from: the National Paediatric Mortality Registry office; Clinical, Cytogenetics and Molecular genetics database; Radiology and the Hospital In-Patient Enquiry system (HIPE). In addition a detailed analysis of national death registration information for RDs from 2006-2016 was undertaken along with a 2year study (2015-2016) of inpatient RD deaths. Results There were 54,789 livebirths in 2000. Genetics records identified 801 cases of RDs Ongoing HIPE searches identified 1381 cases. Mortality data revealed that of all deaths on the Register (2006-2016), (n=4044) aged 0-14, 58.56% (n=2368) had a RD diagnosis with age distribution; Neonates, 56% (1140/2050), Post-neonates, 58% (450/778), Children aged 1-14 years, 64% (778/1216). Of the total (n=234) inpatient deaths with a RD from 2015-2016, 52.6% (n=123) were cared for at the two major centres. Conclusion This study to-date has identified > 2,200 RD patients presenting by age 17 giving a minimum incidence of 4% for paediatric RDs. We expect the final figure to be higher when we complete analysis of all the HIPE and sub-specialty data from these major centres., Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. ADPKD is primarily caused by variants in PKD1 and PKD2. Sequencing of PKD1 is difficult due to multiple pseudogenes. There is unexplained variance in the age-of-onset of PKD, even within families. Aim 1) Establish a targeted NGS panel to improve molecular diagnosis of PKD and 2) characterize large ‘super-families’ for the study of new ADPKD genes and genetic modifiers. Methods NGS was performed using a custom Roche SeqCap targeted panel (273 genes) and Illumina NextSeq. Bioinformatics was performed using an in-house GATK pipeline. Pathogenicity was assigned using American College of Medical Genetics and Genomics guidelines and Mayo Clinic PKD in-house methods. Gap-filling Sanger sequencing was utilized in unsolved cases Results 172 PKD patients were sequenced with average coverage 189X. A molecular diagnosis meeting pathogenicity criteria was obtained in 82% (141/172) of patients following gap-filling Sanger of PKD1 and PKD2 (n=41). 46 of the PKD-causing variants we detected were novel. We identified 13 rare, diagnostic PKD variants shared across multiple affected individuals recorded clinically as having no known familial relationship. Second-degree relatedness was confirmed via clinical follow-up. These families form the basis for the assembly of PKD ‘super-families’. Conclusions NGS is suitable for sequencing of PKD genes including PKD1, although some gap filling by Sanger is required for complete coverage. We have identified 13 potential ADPKD ‘super-families’ using genomic data for further study. These results are improving diagnostics of ADPKD in the Irish renal clinic., Purpose Target5000 is a genetic study to detect and characterise variants associated with inherited retinal degenerations (IRD). Choroideremia is an X-Linked recessive chorioretinal degenerative condition with progressive atrophy of several key cells of the retina and the surrounding blood retinal barrier. Here we describe a novel deletion in the CHM gene found in two Irish pedigrees. This 500kb deletion represents the largest yet detected IRD-associated deletion in Ireland. Approach As part of the Irish IRD registry, Target5000, patients with inherited retinal degenerative conditions are recruited. Target capture sequencing was employed to investigate variation in 254 IRD-associated genes. Upon detection of the deletion in CHM, PCR analysis was used to elucidate the full extent of the deletion. Results Two members of a large X-linked Retinitis Pigmentosa pedigree clinically presented with choroideremia and tested negative for the segregating RPGR variant found in other affected members of this pedigree. Both males were sequenced and found to possess large deletions spanning the CHM gene, totalling 500kb. This deletion has also been detected in a second Irish pedigree since its discovery. Two additional males and two carrier females from this second pedigree were all found to be severely affected with progressive choroideremia. Conclusions Typically, female carriers of CHM mutations show mild stationary signs with no symptoms, while males are severely affected. In this instance, females were more severely affected than expected with advanced signs of degeneration and progressive visual decline. This is possibly due to random X-inactivation and the severity of CHM gene deletion., Introduction The largest cohort of patients at The National Centre for Adult Inherited Metabolic Disorders (NCIMD) have Phenylketonuria (PKU). The NCIMD manages patients transitioned from Paediatric services upon reaching adulthood. Improved treatments have extended life expectancy and increased quality of life for patients with PKU; however diet and supplements remained the only means of treatment for life until the recent introduction of Sapropterin dihydrochloride. Aim To analyse the genotype of the PKU cohort in attendance at The NCIMD with a focus on responsiveness to Sapropterin dihydrochloride. Method The data are collated from when the Adult unit was first established in 2013 until the end of May 2019. Exclusion criteria include patients over the age of 53 and patients who have two negatively indicated genotypes for the use of Sapropterin dihydrochloride. Genotypes are recorded in a secured database onsite and descriptive analyses were performed. Results The total number of patients examined is 282; 104 were male (36.8%) and 178 were female (63.1%). The total samples processed and available for analysis were 148 (male= 46, 31%; female= 102, 68.9%). The frequency of Saptopterin dihydrochloride responsiveness in both alleles was observed (responsive= 15, 10%; unresponsive= 48, 48.33%; uncertain= 85, 57%). The most common alleles recorded were R408W (41.1%), F39L (13.8%), 165T (11.2%), and L249F (3.8%). Conclusion Due to the uncertainty surrounding Sapropterin dihydrochloride responsiveness for various common mutations in the Irish PKU cohort, there is a need for greater genetic and metabolic collaboration. Analysis and treatment may be impacted by time elapsed from sending samples to receiving results., Introduction The Department of Clinical Genetics at CHI provides services for individuals affected by or at risk of a genetic condition in the Republic of Ireland. There are currently 3,283 referrals waiting to be seen, of whom 930 are waiting longer that the HSE standard of 18 months. A negative consequence of a long waiting list is that patients die whilst waiting. Resulting harm includes: 1) no diagnosis 2) no genetic testing, no DNA stored, 3) family unaware of a hereditary disorder, denied screening, 4) relatives having unnecessary screening as no predictive test for family, 5) future pregnancy options limited if paediatric proband undiagnosed. As of 13/06/2019, we have recorded 33 deaths on our waiting list. We began to systematically collect data on deaths since March 2018. This study concentrates on these cases; n=15/33. Aims To identify the consequences to the relatives of these 15 referrals. Results Nine were adult cancer genetic referrals, 5/9 diagnostic, 3/9 predictive, and a further case had NF2. Only 1/9 had DNA stored. Two adult patients had a cardiac family history (Marfan syndrome, cardiomyopathy) respectively. Neither had DNA stored. Four paediatric patients had multiple malformations secondary to a chromosomal or genetic syndrome. In 3/4 a diagnosis had already been reached. The fourth case, who died unexpectedly of unrelated causes, had no DNA stored. Summary 11/15 patients who died did not have DNA stored, precluding diagnosis and risk calculation for their relatives. As each extended 3 generation Irish family has ~64 relatives, lack of diagnosis has far reaching consequences., Background Women who carry a pathogenic variant in either a BRCA1 or BRCA2 gene have a high lifetime risk of developing breast and tubo-ovarian cancer. To manage this risk, women may choose to undergo risk-reducing surgery to remove breast tissue, ovaries and fallopian tubes. Surgery should increase survival, but can impact women’s lives adversely at a psychological and psychosexual level. Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed. Aim of Review To examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life. Methods We searched the Cochrane Central Register of Controlled trials (CENTRAL) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, Web of Science and Scopus up to April 2019. Results We identified two studies; one randomised controlled trial and one nonrandomised study. Conclusions The effect of psychosocial interventions on quality of life and emotional well-being in female BRCA carriers who undergo risk-reducing surgery is uncertain given limited high quality evidence. Next Generation Sequencing, along with targeted cancer treatments, increasing knowledge around the biology of cancers and the results of the 100K Genome Project will open up genetic testing to many more women. For as long as surgical interventions remain the dominant risk-reducing option for management of women with a deleterious BRCA gene, health professionals have a responsibility to ensure there is provision to holistically manage the outcomes of such surgery., Introduction FATCO (Fibular Aplasia, Tibial Campomelia and Oligosyndactyly) syndrome is a rare descriptive diagnosis first defined by Courtens et al. in 2005, who recognised a comparable pattern of malformations with his own case and 4 others described in the literature. Aetiology remains unknown, however defects involved in SHH (Sonic hedgehog) gene expression have been proposed. Case Description We report on a term male infant born with severe malformations. On examination, there was absence of the left radius and ulna, bilateral anterior angulation of lower limbs with skin dimpling overlying. Both ankle joints were dysplastic and there was oligosyndactly of both feet. Right upper limb was normal. X-rays of the limbs revealed dysplastic tibiae, absence of both fibulae, a right foot containing 3 ossified metatarsals with 2 formed digits, and a left foot with a single ossified metatarsal and two soft tissue digits with small bony elements. The infant had no other associated anomalies, and is developmentally appropriate at 1 year. Management included Symes amputation, prosthetics and following genetic referral FATCO syndrome was suggested as the best fitting diagnosis. Whole genome sequencing of the infants blood is currently being performed. Discussion This is an important case to report as there are very few descriptions in the literature, In keeping with the majority of reports, this case appears to be sporadic and development is normal. Our case is male, keeping with preponderance. Treatment aims at optimising functionality of limbs and stabilisations of joints., Introduction Fibrous cephalic plaques (FCP) are a characteristic manifestation of tuberous sclerosis complex (TSC) and occur in one third of cases. Their natural history and long term course is unknown, as is the outcome of long term follow-up of TSC cases in old age. Phenotype and methods We describe an 80 year old with TSC due to a c.2784dupC TSC2 mutation, who was diagnosed in infancy with an FCP and was regularly followed up at the TSC clinic over 8 decades with regular epilepsy treatment and renal monitoring. Results Regular clinical photography and clinical records document the plaque at different ages. The FCP naturally resolved at 74 years. Facial angiofibromas also faded with time in the last decade. His epilepsy and renal abnormalities remained under control with careful surveillance and monitoring. Discussion Natural aging in the eighth decade causes progressive laxity of collagen and leads to natural resolution of FCPs. This novel finding with a unique 80 year follow up yields valuable insights into the aging changes within FCPs and facial angiofibromas as the pathways linking facial angiofibromas and FCP’s through the TGF-β1 pathway are now being elucidated. Conclusion We present a clinical odyssey showing the natural progression and history of FCPs in TSC and comment on the mechanistic pathways allowing potential interventions in this disfiguring condition. TSC cases can be successfully managed and complications – particularly in the brain and kidney, can be avoided over an entire lifetime. This is encouraging for long term prospects for patients with TSC., Introduction Fabry disease is an X-linked inherited disorder due to deficient activity of the enzyme alpha-galactosidase A and progressive lysosomal deposition of globotriaosylceramide in cells. Aim To report the genotype/phenotype landscape of the adult Fabry disease cohort attending The National Centre for Adult Inherited Metabolic Disorders (NCIMD). Method All Fabry patients (N=70) attending NCIMD until end of May 2019 were included in this analysis. Genotypes and phenotypes were recorded by chart review. Descriptive analyses were performed. Result 26 (37.1%) were male (median age 43 [32:54]) and 44 (62.9%) were female (median age 46 [25:61]). The AGAL pathogenic variants were missense (52, 74.3%), deletion (9, 12.9%), nonsense (8, 11.4%) and duplication (1, 1.4%). Most missense variants occurred in exon 2 (25%), exon 3 (19.2%), exon 5 (23.1%) and exon 6 (21.2%). 21.2% of missense variants were N215S. 28 patients were on enzyme therapy and 2 were on oral chaperone therapy. The incidence of cardiac (M=18/26; F=18/44; p=0.021), renal (M=14/26; F=18/44; p=0.304), neurological (M=17/26; F=20/44; p=0.107) and hearing (M=14/26; F=19/44; p=0.399) involvement were observed. Within N215S cohort, 2 had hypertrophic cardiomyopathy and 5 with a degree of left ventricular hypertrophy. Conclusion Pathogenic variants were observed across the AGAL gene in the cohort. Incidence of cardiac involvement in both genders is similar. Females had more frequently observed renal, neurological and hearing involvement. N215S AGAL variant is the most common variant which is associated with a predominant cardiac phenotype, thus collaboration between clinical geneticists and cardiovascular physicians are important when establishing diagnosis and management., Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a worldwide prevalence of 1:500. Genetic etiology is suspected in up to 50% of HCM patients. To gain insight into the diagnostic yield and mutation spectrum of HCM, a retrospective review was performed for 114 consecutive cases with a clinical suspicion of HCM who underwent multigene panel testing at our laboratory between 2014 and 2019. Method Data was manually extracted from laboratory reports with respect to indication for testing, number of genes on panel, variants identified and classification at the time of testing. Results A total of 114 patients with a diagnosis of HCM had samples submitted for diagnostic testing using a multigene panel of between 16 and 20 genes, depending on the year of testing. 56 patients had no genetic variant identified, 33 patients had a pathogenic or likely pathogenic variant identified and 25 had a variant of uncertain significance identified. One 11 year old patient had a normal result from an 18 gene panel for HCM, but was later diagnosed with Friedrich ataxia. One adult female patient had a normal result from a 19 gene panel but was later diagnosed with Fabry disease. Conclusion Clinically actionable ‘Pathogenic’ or ‘Likely pathogenic’ variants were identified in 29% of patients with a Clinical diagnosis of Hypertrophic Cardiomyopathy with VUS being identified in 22%. The most common 2 genes in which clinically actionable variants were found were MYH7 (47%) and MYBPC3 (31%)., Huntington’s disease (HD) is an inherited progressive neurodegenerative condition. In the Republic of Ireland genetic testing for HD is available via two routes. Symptomatic individuals can access testing via a Neurologist. Asymptomatic individuals with a known family history of HD can seek testing via a genetic counselling multi-step process. Aim The aim of the audit was to review the activity of the HD specialty clinic. Methods Retrospective chart, laboratory and clinical database review for HD referrals received for 2016, 2017 and 2018 was carried out. Parameters examined included: number of referrals, age profile, motivation for testing, results. Results Over this 3 year period 93 referrals were received. 80 referrals were for predictive testing and 13 for genetic counselling post testing through neurology. The youngest person was 18 years of age at time of referral. More females requested a referral for predictive testing than males, 48 (60%) and 32 (40%) respectfully. The most common motivation given for predictive testing was with regard to family planning and concerns for children and to help them plan for the future. Of the 30 tests carried out to date, 52% were mutation positive and 42% were mutation negative. The average age of those who proceeded with testing was 37yrs. Conclusion These findings reflect data published from the UK with regard to age of presentation and female to male bias. The most common motivation for testing was family planning unlike the UK where the most common reason provided was to reduce uncertainty.
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- 2020
6. Efficacy of a Medical Directive to Reduce Inappropriate Indwelling Urinary Catheter Use on Orthopedic Wards
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Jina, R., Foley, L., Chan, S., Wong, E., Ward, S., Kuan, D., Wong, C., Wang, S-J., Lee, L., Hammond, M., Leu, R., Cuperfain, A., Perrella, A., Canfield, A., Woo, T., McCollum, A., Landry, V., Yetman, L., Theou, O., Andrew, M., Jarrett, P., Arya, R., Cristancho, S., Thain, J., Diachun, L., Tsui, C., Kim, K., Spencer, M., Reich, K., Moledina, A., Kwan, E., Keir, M., Fan, B.J.Y., Wong, R.Y.M., Reppas-Rindlisbacher, C., Lee, J., Siddhpuria, S., Gabor, C., De Freitas, S., Khalili, Y., Curkovic, A., Patterson, C., Naqvi, R., Wong, C.L., Koo, K., To, E., Stoian, M., Tung, J., Benjamin, S., Ho, J., Burrell, A., Chahine, S., Casey, G., Kekewich, M., Swain, K., Pridham, A., Morgan, A., Wilding, L., Moors, J., Khoury, L., Jabbar, A., Costa, A., Jafri, A., Osborne, A., Cowan, D., Onge, J. St., Pieruccini-Faria, F., Bray, N., Montero-Odasso, M., Abou-Sharkh, A., Mayo, N., Wall, M., Harvey, E., St-Jean, S., Albers, A., Bergeron, S., Bérubé, P., Morin, S., Turner, J., Martin, P., Zhang, Y.Z., Tannenbaum, C., Pulok, M., van der Valk, A., Rockwood, K., Dearing, M., Bowles, S., Isenor, J., Reeve, E., Piankova, P., Eintracht, S., Hoffer, L.J., Afilalo, J., Mate, K., Morais, J., Ahmed, U., Akter, R., Maksymowych, W., Martin, L., Hogan, D., Alston, J., Gandell, D., Cheung, E., Arora, R., Kundid, E., Ali, A., Martin, G., Versloot, J., Bartholomew, S., Robitaille, C., Plebon-Huff, S., Beauchet, O., Fung, S., Launay, C., Chabot, J., Galery, K., Dejager, S., Bineau, S., Berrut, G., Bobrowski, C., Brown, D., Contreras, J., Norris, M., Jaunkalns, R., Liu, B., Chertkow, H., Borrie, M., Feldman, H., Whitehead, V., Rylett, J., McGilton, K., Black, S., Masellis, M., Chuen, V., Chan, A., Alibhai, S., Chau, V., Church, S., Rogers, E., Squires, E., Colborne, A., Fenwick, P., Cahill, L., Collier-Jarvis, Krista, Mah, Jasmine, Cullen, S., Carroll, S., Cuthbertson, L.R., Stajduhar, K., Cloutier, D., Day, A., Ng, K., Dubé, J., Truemner, J., Best, S., Sargeant, P., Faisal, S., Ivo, J., McDougall, A., Bauer, J., Pritchard, S., Chang, F., Patel, T., Faulkner, C., Bronskill, S., Rosella, L., Stall, N., Savage, R., Zhu, L., Manuel, D., Rochon, P., Godin, J., Black, K., McNeil, S.A., Andrew, M.K., Gong, Z., Song, H., Thrall, S., Wang, X.M., Allaby, C., Papaioannou, A., Gorman, M., MacGrath, M., Haddad, S.M. Hassan, Scott, C.J.M., Arnott, S.R., Ozzoude, M., Swartz, R.H., Mandzia, J., Kwan, D., Beaton, D., Bartha, R., Harasym, P., Brisbin, S., Quail, P.B., Venturato, L., Sinnarajah, A., Virk, N., Kaasalainen, S., Sussman, T., Hanson, H., Sharon, S., Holroyd-Leduc, J., Haslam, L., DePaul, V., Woo, K., Donnelly, C., Auais, M., Haviva, C., Zimmer, Z., Jacob, K., Sonjak, V., Hajj, G., Chevalier, S., Lamarche, M., Janower, A., John, P. St., Jayanama, K., Jeffrey, E., Ji, A. (Tianshu), McGregor, M., Kow, J., Kehler, S., Giacomantonio, N., Firth, W., Blanchard, C., Kelly, S., Lorbergs, A., Crilly, R., Knoefel, F., Sabra, I., Wallace, B., Breau, M., Sweet, L., Goubran, R., Frank, A., Kokorelias, K., Cronin, S., Eftekhar, P., Munce, S., Jagal, S., Vellani, S., Wang, C., Salbach, N., Colella, T., Kontos, P., Grigorovich, A., Chau, B., Cameron, J., Krause, K., Lam, K., Arnold, C., Wu, W., Piggott, K., Parikh, R., Hillier, L.M., Lu, S.K., Gevaert, V., Walker, S., Lu, S., Wong, W., Gregg, S., Bedirian, W., Skimson, K., Milligan, J., Lovett, M., Negm, A., Ioannidis, G., Petruccelli, D., Winemaker, M., Luthra, A.S., de Jesus, I.T. Machado, Gratão, A.C. Martins, Nascimento, C.M. Crispim, de Souza Orlandi, F., de Oliveira Gomes, G.A., Say, K. Gramani, dos Santos, A. Angelini, Cominetti, M.R., Pavarini, S.C. Iost, Zazzetta, M.S., Madden, Ken, Feldman, Boris, Meneilly, Graydon, Makhani, A., Qureshi, S., Hunter, K.F., Wagg, A., Gibson, W., Marion, M., Monor, A., Malik, S., O’Donoghue, C., Marr, S., Wilson, J. McKinnon, Doleweerd, J., Berezny, T., Mayo, A., Senechal, M., Boudreau, J., Belanger, M., Bouchard, D., McGarrigle, L., Wallace, L., Howlett, S.E., Mehta, N., Ghuman, I., Mehta, M., Brode, S., Mehrabi, M., Marras, T., Mele, B., Merrikh, D., Ismail, Z., Goodarzi, Z., Mercer, S., Babb, K., Nauth, S., Tait, G., Liberman, D., Devine, L., Nepal, R.M., Vojicic, J., Dion, S., Major, M., Isturiz, R.E., Nguyen, Q. Dinh, Nicholson, K., Fortin, M., Griffith, L., Terry, A., Williamson, T., Mangin, D., Stranges, S., Pageau, F., van der Horst, M-L., McArthur, C., Jain, R., Jaglal, S., Adachi, J.D., Giangregorio, L., Parmar, J., Brémault-Phillips, S., Duggleby, W., Charles, L., Tian, P.G. Jaminal, Bedaba, R., Rolfson, D., Torti, J., Dobbs, B., Khera, S., Abbasi, M., Chan, K., Carr, F., Triscott, J., Huang, J., Moores, D., Cerna, J., Jamieson, J., Jensen, L., Johnson, C., Chow, J., Guzak, J., Mathura, P., Sun, X., Pearce, P., Dempsey, E., Mahon, A., Pérez-Zepeda, U., Borda, M-G., Almeda-Valdés, P., Cesari, M., Peters, M-L., Davidson, S., Reece, K., Spira, N., Uranis, C., Whelan, L., Ryan, D.P., Brown, D.M., Saha, A., Thiyagalingam, S., Wachtel, J., Ramasamy, D., Schmidt, K., Nobleza, S., Gordon, C., Hung, M., Thangaraja, M., Searle, S.D., Ellis, H. Logan, Ramlakhan, D., Davis, D., Sekhon, H., Sepehri, K., Song, X., Chinda, B., Braley, M., Zou, M., Tang, B., Garm, A., Park, G., Sirisegaram, L., Sarquis-Adamson, Y., Smallbone, J., Posner, A., Yogaparan, T., Kelly, R., Singh, S., Keetch, K., Heiazi, S., Sandercock, J., Shyr, C., D’Arcy, R., McDermid, R., Clarke, B., Hanson, C., Tate, R., Shah, N., Resnick, J., Amin, S., Manzoor, S., Mistry, N., Fless, K., Rezai, F., Ovnanian, V., Yodice, P., Torbiak, L., Schmaltz, H., Trenaman, S., Kirkland, S., Bodkin, R. J., Wang, K., Ganesh, V., Neat, C., Raber, C., An, H., Beyzaei, N., Lau, C., Lee, F., Cox, L., McElhaney, J., McNeil, S., Wong, T., McKellar, L., Dasgupta, M., Vasudev, A., Burhan, A., O’Regan, N., Yeung, C., Srinathan, S., and Dhaliwal, R.
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Abstracts ,Geriatrics and Gerontology ,Gerontology - Published
- 2019
7. Additional file 1 of Exploring utilisation of the allied health assistant workforce in the Victorian health, aged care and disability sectors
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Huglin, J., Whelan, L., McLean, S., Greer, K., Mitchell, D., Downie, S., and Farlie, M. K.
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Data_FILES - Abstract
Additional file 1.
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- 2021
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8. Efficacy and safety of fesoterodine 8 mg in subjects with overactive bladder after a suboptimal response to tolterodine ER
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Kaplan, S. A., Cardozo, L., Herschorn, S., Grenabo, L., Carlsson, M., Arumi, D., Crook, T. J., Whelan, L., Scholfield, D., and Ntanios, F.
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- 2014
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9. Pierre Bonnard: beyond visual perception
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Whelan, L and Grootenboer, H
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History of modern art - Abstract
This thesis presents a new understanding of modern art history through the French artist Pierre Bonnard (1867-1947). Refuting the prevailing realist understanding of his work, it shows how Bonnard developed original strategies for expanding depiction beyond a transcription of the world as it appears to vision – an aim that was central to artistic innovation in the early twentieth century.
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- 2020
10. Breaking barriers to research skills training and enabling access to those who need it the most
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Boggs, L, Whelan, L, Segrt, A, and Lang, T
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- 2020
11. Community Rehabilitation Stroke Audit: 000
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Whelan, L, Greer, K, and Rangarajan, P
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- 2012
12. Applications of SELDI-MS technology in oncology
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Whelan, L. C., Power, K. A. R., McDowell, D. T., Kennedy, J., and Gallagher, W. M.
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- 2008
13. Effect of posture on body temperature of young men in cold air
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Donaldson, G. C., Scarborough, M., Mridha, K., Whelan, L., Caunce, M., and Keatinge, W. R.
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- 1996
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14. Use of the AnaConDa™ anaesthetic delivery system in ICU
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Whelan, L.
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- 2007
15. Serving on an enquiry panel: one nurse's experience
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Whelan, L.
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- 2002
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16. PERSON-CENTERED LANGUAGE FOR RESPONSIVE BEHAVIOURS
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Peters, M., primary, Brown, D., additional, Whelan, L., additional, Davidson, S., additional, Uranis, C., additional, Reece, K., additional, and Spira, N., additional
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- 2017
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17. Analysis of Factors Influencing Outcomes of Full and Partial Hand Multi-articulating Prostheses
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Whelan, L., primary and Wagner, N., additional
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- 2016
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18. Advancements in Partial Hand Prostheses: A Case Study
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Whelan, L., primary
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- 2016
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19. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia
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Pauer, L, Winkelmann, A, Arsenault, P, Jespersen, A, Whelan, L, Atkinson, G, Leon, T, Zeiher, B, Gerli, Roberto, and A0081100investigators
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Adult ,Male ,Sleep Wake Disorders ,Fibromyalgia ,Immunology ,Pregabalin ,Placebo ,law.invention ,Placebos ,Young Adult ,Rheumatology ,Randomized controlled trial ,Double-Blind Method ,law ,Surveys and Questionnaires ,medicine ,Immunology and Allergy ,Humans ,Adverse effect ,gamma-Aminobutyric Acid ,Aged ,Aged, 80 and over ,Sleep disorder ,Analgesics ,business.industry ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Outcome ,Anesthesia ,Female ,medicine.symptom ,business ,Sleep ,Somnolence ,medicine.drug - Abstract
Objective.To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.Methods.This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function.Results.Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (−0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score −5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events.Conclusion.Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registryNCT00333866).
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- 2011
20. The association between exaggeration in health related science news and academic press releases: retrospective observational study
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Sumner, P., primary, Vivian-Griffiths, S., additional, Boivin, J., additional, Williams, A., additional, Venetis, C. A., additional, Davies, A., additional, Ogden, J., additional, Whelan, L., additional, Hughes, B., additional, Dalton, B., additional, Boy, F., additional, and Chambers, C. D., additional
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- 2014
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21. 26 The Effect of Inpatient Occupancy on Emergency Department Door-to-Admit Time: A Mathematical Model Using Spline Regression
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Haas, T., primary, Ondak, S., additional, Whelan, L., additional, Brantley, M., additional, Arthur, A.O., additional, and Thomas, S.H., additional
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- 2014
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22. Non-invasive ventilation outside the intensive care unit for acute respiratory failure: the perspective of the general ward nurses
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Cabrini, L., Giacomo Monti, Villa, M., Pischedda, A., Masini, L., Dedola, E., Whelan, L., Marazzi, M., and Colombo, S.
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- 2009
23. Chapter 44 Cellular and molecular models of neuron-matrix adhesion in nerve fiber growth
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Carbonetto, S., primary, Harvey, W.J., additional, Douville, P.J., additional, and Whelan, L., additional
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- 1988
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24. TISSUE CROSS-REACTIVITY OF MOUSE AND HUMAN MONOCLONAL AND POLYCLONAL ANTIBODIES AGAINST HUMAN ORBITAL TISSUE ANTIGENS
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Kuroki, T., primary, Kodama, K., additional, Whelan, L., additional, and Wall, J.R., additional
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- 1985
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25. The Ultra-Performance Liquid Chromatography Determination of Domperidone and Its Process-Related Impurities
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Curtin Whelan, L., primary, Geary, M., additional, Wharton, M., additional, and Sweetman, P., additional
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- 2014
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26. 585 Responders and partial responders to tolterodine extended release: Effect of fesoterodine in tolterodine partial responders
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Ntanios, F., primary, Carlsson, M., additional, Arumi, D., additional, Whelan, L., additional, and Scholfield, D., additional
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- 2014
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27. Brachypodium distachyonCell Suspension Cultures: Establishment and Utilisation
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Hunt, D., primary, Chambers, J.P., additional, Behpouri, A., additional, Kelly, S.P., additional, Whelan, L., additional, Pietrzykowska, M., additional, Downey, F., additional, McCabe, P.F., additional, and Ng, C.K.-Y., additional
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- 2014
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28. Evaluating Fatigue in Fibromyalgia: Development and Validation of the Daily Diary of Fatigue Symptoms in Fibromyalgia (DFS-Fibro)
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Burbridge, C., primary, Symonds, T., additional, Humphrey, L., additional, Arbuckle, R., additional, Hirsch, I., additional, and Whelan, L., additional
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- 2013
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29. Magnetic Bearings, Variable Speed Centrifugal Compression And Digital Controls Applied In A Small Tonnage Refrigerant Compressor Design
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Conry, R., Whelan, L., and Ostman, J.
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- 2002
30. Family Practice is seeking excellent manuscript submissions
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Neale, A. V., primary and Whelan, L., additional
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- 2013
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31. 740 A randomised controlled trial of fesoterodine in subjects with overactive bladder and suboptimal response to tolterodine extended release: Results from the AFTER study
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Cardozo, L., primary, Kaplan, S., additional, Herschorn, S., additional, Grenabo, L., additional, Carlsson, M., additional, Arumi, D., additional, Crook, T.J., additional, Whelan, L., additional, and Ntanios, F., additional
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- 2013
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32. 112 A Pilot Study Investigating the Use of Heated Humidified Oxygen and Dry Oxygen Therapy in Children with Acute Respiratory Illness
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Whelan, L., primary and McCall, E., additional
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- 2012
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33. Fibromyalgia patients: similar pattern of baseline diagnosis characteristics across regions
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Murphy, K., primary, Zeiher, B., additional, Atkinson, G., additional, Whelan, L., additional, and Pauer, L., additional
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- 2009
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34. Long-term safety and tolerability of pregabalin treatment in three open-label extension studies in patients with fibromyalgia
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Murphy, K., primary, Zeiher, B., additional, Herman, B., additional, Atkinson, G., additional, Pauer, L., additional, and Whelan, L., additional
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- 2009
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35. P.8.a.022 Do European patients with fibromyalgia respond differently than others to pregabalin? A 14-week monotherapy trial
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Pauer, L., primary, Whelan, L., additional, Atkinson, G., additional, Leon, T., additional, and Zeiher, B.G., additional
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- 2008
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36. A reply
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Whelan, L., primary
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- 2007
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37. High Quality Aluminide and Thermal Barrier Coatings Deposition for New and Service Exposed Parts by CVD Techniques
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Pedraza, F., primary, Tuohy, C., additional, Whelan, L., additional, and Kennedy, A.D., additional
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- 2004
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38. Oral control and body dissatisfaction in older adults: a note of caution
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Davies, A. D. M., primary, Whelan, L., additional, and King, D., additional
- Published
- 2000
- Full Text
- View/download PDF
39. PND48 - Evaluating Fatigue in Fibromyalgia: Development and Validation of the Daily Diary of Fatigue Symptoms in Fibromyalgia (DFS-Fibro)
- Author
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Burbridge, C., Symonds, T., Humphrey, L., Arbuckle, R., Hirsch, I., and Whelan, L.
- Published
- 2013
- Full Text
- View/download PDF
40. A feasibility study of videotaping to assess the relationship between distress in Alzheimer's disease caregivers and their interaction style
- Author
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GALLAGHER-THOMPSON, D., primary, CANTO, P. G. DAL, additional, DARNLEY, S., additional, BASILIO, L. A., additional, WHELAN, L., additional, and JACOB, T., additional
- Published
- 1997
- Full Text
- View/download PDF
41. Entry-level OTR and COTA intervention utilization derived from NBCOT practice analysis: implications for fieldwork experiences.
- Author
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Crist PA, Brown LI, Fairman A, Whelan L, and McClure L
- Abstract
Effective fieldwork provides students with learning experiences in preparation for entry-level practice as occupational therapists (OT) or occupational therapy assistants (OTA). In 2003, the National Board for Certification in Occupational Therapy, Inc.® (NBCOT) con-ducted a practice analysis of entry-level certified occupational therapy practitioners (OTR & COTA) to validate a test blueprint for the national certification examinations. This study reports a novel, elective survey reflecting the total percentage of entry-level practitioners, who reported use of 88 different interventions.The purpose of this paper is to translate the practice analysis intervention data gathered in the optional survey to plan and implement effective fieldwork that prepares fieldwork students for entry-level practice. The results of this study will provide understanding of intervention use among entry-level practitioners (OTR = 479; COTA = 168) as a function of practice context. An initial correlation of a random sample of 100 OTRs and COTAs found group equivalency, meaning that the OTR information could be used for the major analyses and generalized to include COTA. Fourteen interventions were found commonly across all practice settings for OTR. These fourteen were factored into three areas or themes (preparatory and activities of daily living; motor skills, posture and coordination; and mental functions) with significant frequency of intervention utilization. Further analysis indicated a high variability of the top thirty interventions for each setting with regard to utilization of interventions above and below the 50 percentile.This snapshot of practice regarding entry-level intervention utilization in occupational therapy across seven major practice settings is described and application to fieldwork processes elaborated. The in-formation provides a description of practice in each setting that can be used by academic fieldwork coordinators for student placement decisions. Fieldwork educators can use this information as a guide for planning comprehensive fieldwork-learning activities, as well as supervising students. Fieldwork students can use this intervention utilization information to assess their readiness for entry-level practice in each setting. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
42. Antithyroglobulin monoclonal and autoantibodies cross-react with an orbital connective tissue membrane antigen: a possible mechanism for the association of ophthalmopathy with autoimmune thyroid disorders.
- Author
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Kuroki, T., Ruf, J., Whelan, L., Miller, A., and Wall, J. R.
- Subjects
IMMUNOGLOBULINS ,ANTIGENS ,IMMUNITY ,ORGANS (Anatomy) ,BLOOD plasma ,LIVER - Abstract
The possibility that Graves' ophthalmopathy and autoimmune thyroid disorders may be associated because of autoimmune reactions against antigens shared between human orbital and thyroid tissues was investigated using anti-thyroglobulin (Tg) monoclonal and autoantibodies. Eleven of 16 mouse monoclonal antibodies (MCAB) tested reacted, in an enzyme-linked immunosorbent assay (ELISA), with an antigen in human orbital connective tissue membranes (OCTmem), but not with the OCT soluble fraction, or with membrane or soluble fractions of human eye muscle, lacrimal gland or skin connective tissue. The anti-OCTmem activity was absorbed by OCTmem and Tg, but not by liver membranes or bovine serum albumin (BSA). In preliminary studies four out of 113 human MCAB against thyroid or orbital tissue antigens showed reactivity restricted to Tg and OCTmem. Sera from approximately 50% of patients with autoimmune thyroid disorders, with or without ophthalmopathy, also reacted with OCTmem. The autoantibody activity correlated closely with serum titres of antithyroglobulin but not with the presence, duration, or severity of the eye disease. The OCTmem reactivity was absorbed by Tg, thyroid membranes, and OCTmem but not liver membranes, membranes prepared from other orbital tissues, or BSA. The OCTmem-Tg shared antigen site appeared not to be native thyroglobulin since, (i) MCAB and serum autoantibodies did not react with the cytosol fraction of OCT, and (ii) because the membrane antigen was not solubilizable. Because not all patients with ophthalmopathy have detectable anti-Tg antibodies and, conversely, because not all patients with detectable anti-Tg antibodies develop opthalmopathy it is unlikely that autoimmunity against a OCTmem-Tg shared antigen is the primary mechanism of Graves' ophthalmopathy, although this possibility has not been excluded. On the other hand the reaction of anti-Tg autoantibodies with OCT membranes may be a model for other autoimmune reactions against other thyroid-orbital tissue-shared antigens. While the pathogenesis of Graves' ophthalmopathy is likely to be multifactorial, humoral and cellular reactions against primary orbital antigens, thyroid-orbitol tissue shared antigens, or both, are likely to play important roles. [ABSTRACT FROM AUTHOR]
- Published
- 1985
43. A feasibility study of videotaping to assess the relationship between distress in Alzheimer's disease caregivers and interaction style.
- Author
-
Gallagher-Thompson, D., Dal Canto, P. G., Darnley, S., Basilio, L. A., Whelan, L., and Jacob, T.
- Subjects
CAREGIVERS ,CARE of Alzheimer's patients ,INTERACTION (Philosophy) ,HEALTH - Abstract
This paper reports the results of an observational study of 15 spouse dyads where the wife was the caregiver and the husband was the care-receiver, diagnosed with 'probable Alzheimer's disease'. Couples were videotaped in their home interacting in an unstructured mealtime, and a structured planning task. Videotaped observations were coded according to the Marital Interaction Coding System (MICS). Summary data from the MICS were correlated with caregiver self-report measures of stress, depression, burden, coping styles, and family environment. A significant correlation was found between the level of conflict in the marriage and the frequency of positive codes observed in the wife during the observations. Several other correlations, while not significant at the 0.05 level, fell in the expected direction. Limitations of this study, and suggestions for future research, are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1997
- Full Text
- View/download PDF
44. 70. The Effect of Common Salt on the Growth of Lactic Streptococci in Milk.
- Author
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McDowall, F. H. and Whelan, L. A.
- Published
- 1933
- Full Text
- View/download PDF
45. 55. The Distribution of Salt in Cheddar Cheese.
- Author
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McDowall, F. H. and Whelan, L. A.
- Published
- 1932
- Full Text
- View/download PDF
46. The base status of Scottish soils: II. Further studies of the effects of lime on typical soils from north-east Scotland.
- Author
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Whelan, L. A.
- Published
- 1939
- Full Text
- View/download PDF
47. 22. Methods of Estimation of Salt in Cheese.
- Author
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McDowall, F. H. and Whelan, L. A.
- Published
- 1931
- Full Text
- View/download PDF
48. 201. The solubility of Cheddar cheese curd in sodium chloride solutions.
- Author
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McDowall, F. H. and Whelan, L. A.
- Published
- 1938
- Full Text
- View/download PDF
49. High quality aluminide and thermal barrier coatings deposition for new and service exposed parts by CVD techniques
- Author
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Fernando Pedraza, Tuohy, C., Whelan, L., and Kennedy, A. D.
50. PND48 Evaluating Fatigue in Fibromyalgia: Development and Validation of the Daily Diary of Fatigue Symptoms in Fibromyalgia (DFS-Fibro)
- Author
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Burbridge, C., Symonds, T., Humphrey, L., Arbuckle, R., Hirsch, I., and Whelan, L.
- Full Text
- View/download PDF
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