81 research outputs found
Trigonometry of spacetimes: a new self-dual approach to a curvature/signature (in)dependent trigonometry
A new method to obtain trigonometry for the real spaces of constant curvature
and metric of any (even degenerate) signature is presented. The method
encapsulates trigonometry for all these spaces into a single basic
trigonometric group equation. This brings to its logical end the idea of an
absolute trigonometry, and provides equations which hold true for the nine
two-dimensional spaces of constant curvature and any signature. This family of
spaces includes both relativistic and non-relativistic homogeneous spacetimes;
therefore a complete discussion of trigonometry in the six de Sitter,
minkowskian, Newton--Hooke and galilean spacetimes follow as particular
instances of the general approach. Any equation previously known for the three
classical riemannian spaces also has a version for the remaining six
spacetimes; in most cases these equations are new. Distinctive traits of the
method are universality and self-duality: every equation is meaningful for the
nine spaces at once, and displays explicitly invariance under a duality
transformation relating the nine spaces. The derivation of the single basic
trigonometric equation at group level, its translation to a set of equations
(cosine, sine and dual cosine laws) and the natural apparition of angular and
lateral excesses, area and coarea are explicitly discussed in detail. The
exposition also aims to introduce the main ideas of this direct group
theoretical way to trigonometry, and may well provide a path to systematically
study trigonometry for any homogeneous symmetric space.Comment: 51 pages, LaTe
The effectiveness of recruitment strategies on general practitioner’s survey response rates – a systematic review
Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care
<p>Abstract</p> <p>Background</p> <p>Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers' and participants' experiences of its implementation and to inform future strategies to maximise recruitment and retention.</p> <p>Methods</p> <p>In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection.</p> <p>Results</p> <p>We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners' contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention.</p> <p>Conclusion</p> <p>Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.</p> <p>Trial registration</p> <p>ISRCTN24081411</p
GalNAc glycoprotein expression by breast cell lines, primary breast cancer and normal breast epithelial membrane
Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of the lectin from Helix pomatia (HPA), is associated with metastatic competence and poor patient prognosis in a range of human adenocarcinomas. These glycoproteins remain poorly characterised, and their functional role has yet to be elucidated. This study describes characterisation of a range of human breast/breast cancer cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of interest, and their comparison with normal breast epithelium and a range of clinical breast carcinoma samples. Confocal and light microscopy studies revealed cytochemical HPA-binding patterns consistent with a fundamental disruption in normal glycobiosynthetic pathways attending increasing metastatic potential. We report the most complete comparative analysis of HPA-binding ligands from cultured breast cells, clinical breast carcinoma samples and normal breast epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein bands common to both clinical tumour samples and breast cell lines and 6 of these bands were also expressed by samples of normal breast epithelium, albeit at much lower levels. Moreover, very marked quantitative but not qualitative differences in levels of expression consistent with metastatic capability were noted. © 2001 Cancer Research Campaignhttp://www.bjcancer.co
Identification of O-Linked Glycoproteins Binding to the Lectin Helix pomatia Agglutinin as Markers of Metastatic Colorectal Cancer
Background
Protein glycosylation is an important post-translational modification shown to be altered in all tumour types studied to date. Mucin glycoproteins have been established as important carriers of O-linked glycans but other glycoproteins exhibiting altered glycosylation repertoires have yet to be identified but offer potential as biomarkers for metastatic cancer.
Methodology
In this study a glycoproteomic approach was used to identify glycoproteins exhibiting alterations in glycosylation in colorectal cancer and to evaluate the changes in O-linked glycosylation in the context of the p53 and KRAS (codon 12/13) mutation status. Affinity purification with the carbohydrate binding protein from Helix pomatia agglutinin (HPA) was coupled to 2-dimensional gel electrophoresis with mass spectrometry to enable the identification of low abundance O-linked glycoproteins from human colorectal cancer specimens.
Results
Aberrant O-linked glycosylation was observed to be an early event that occurred irrespective of the p53 and KRAS status and correlating with metastatic colorectal cancer. Affinity purification using the lectin HPA followed by proteomic analysis revealed annexin 4, annexin 5 and CLCA1 to be increased in the metastatic colorectal cancer specimens. The results were validated using a further independent set of specimens and this showed a significant association between the staining score for annexin 4 and HPA and the time to metastasis; independently (annexin A4: Chi square 11.45, P = 0.0007; HPA: Chi square 9.065, P = 0.0026) and in combination (annexin 4 and HPA combined: Chi square 13.47; P = 0.0002).
Conclusion
Glycoproteins showing changes in O-linked glycosylation in metastatic colorectal cancer have been identified. The glycosylation changes were independent of p53 and KRAS status. These proteins offer potential for further exploration as biomarkers and potential targets for metastatic colorectal cancer
Tumour-associated carbohydrate antigens in breast cancer
Glycosylation changes that occur in cancer often lead to the expression of tumour-associated carbohydrate antigens. In breast cancer, these antigens are usually associated with a poor prognosis and a reduced overall survival. Cellular models have shown the implication of these antigens in cell adhesion, migration, proliferation and tumour growth. The present review summarizes our current knowledge of glycosylation changes (structures, biosynthesis and occurrence) in breast cancer cell lines and primary tumours, and the consequences on disease progression and aggressiveness. The therapeutic strategies attempted to target tumour-associated carbohydrate antigens in breast cancer are also discussed
Managing hyperemesis gravidarum: a multimodal challenge
Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect
The use of brief screening instruments for age-related cognitive impairment in New Zealand
This study aimed to determine which measures are most commonly used to screen for age-related cognitive impairment in New Zealand, to describe how and why they are used, determine the factors clinicians deem most important in the selection of a particular screen and their levels of training and expertise in using particular screens. A web survey was completed by geriatricians, neurologists, psychiatrists, and psychologists (N=82). Cognitive screening measures were selected for the survey based on previous research. According to the sample, the most frequently used screen was the Mini-Mental State Exam (MMSE), followed by the Clock Drawing Test (CDT) and Addenbrooke's Cognitive Examination Revised (ACE-R). Cognitive screening fulfilled a variety of functions in clinical practice and was widely used, especially in services for older people, however formal training was limited. Availability, reliability and validity, and brevity (respectively) were the most important factors clinicians considered when selecting a screening instrument. Respondent comments agreed with current literature that the MMSE is inadequate as a screening instrument for cognitive impairment, and this was reflected in the comments of respondents on the survey questionnaire, yet this was still the most commonly used measure in New Zealand.falsePublishe
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