Biomedical subjects

Richard Williams

Publications and source records attributed to Richard Williams.

23 records · Page 2Linked to original sources

PubMed2003

Responding to nursing's agenda for the future. Where do we stand on recruitment and retention?

How can the nursing profession address the escalating shortage of registered professional nurses? A multifaceted approach is important to ensure success. One domain of Nursing's Agenda for the Future (American Nurses Association [ANA], 2002) is recruitment and retention. Through the Agenda, creative strategies are being sought to attract and retain qualified nurses. This article describes one institution's response to addressing this critical shortage. Strategies were developed to present a continuum of learning and advancement opportunities across the career span of the professional nurse. They include recruiting student nurses, increasing NCLEXRN pass rates, providing financial support for further education or specialty certification, and using shared governance to increase retention. Institutions must look to their own resources as well as federal and state resources to offer these opportunities to nursing staff. The goal is to build an environment that both attracts nurses and supports them in their career and life goals.

Career Mobility↗

PubMed2002

Chromosome 1q expression profiling and relapse in Wilms' tumour.

Gene-expression patterns have proved useful for tumour classification and prediction of prognosis. We investigated a new gene-expression profiling method that targets individual chromosomes--comparative expressed sequence hybridisation (CESH)--to establish if any expression pattern was associated with relapse, and if this pattern could accurately predict outcome. We studied 18 cases of Wilms' tumour with favourable histological findings. Relative overexpression of genes on the long arm of chromosome 1 was shown in all tumours that subsequently relapsed but in none of those from patients in remission (odds ratio 357, 95% CI 6.4-19960). This finding shows the value of CESH analysis to rapidly screen for chromosomal regions that carry genes whose differential expression is important in establishment of tumour behaviour.

Child↗

PubMed2002

Rate acceleration of the Baylis-Hillman reaction in polar solvents (water and formamide). Dominant role of hydrogen bonding, not hydrophobic effects, is implicated.

A substantial acceleration of the Baylis-Hillman reaction between cyclohexenone and benzaldehyde has been observed when the reaction is conducted in water. Several different amine catalysts were tested, and as with reactions conducted in the absence of solvent, 3-hydroxyquinuclidine was found to be the optimum catalyst in terms of rate. The reaction has been extended to other aldehyde electrophiles including pivaldehyde. Attempts to extend this work to acrylates was only partially successful as rapid hydrolysis of methyl and ethyl acrylates occurred under the base-catalyzed and water-promoted conditions. However, tert-butyl acrylates were sufficiently stable to couple with relatively reactive electrophiles. Further studies on the use of polar solvents revealed that formamide also provided significant acceleration and the use of 5 equiv of formamide (optimum amount) gave faster rates than reactions conducted in water. Using formamide, further acceleration was achieved in the presence of Yb(OTf)(3) (5 mol %). The scope of the new conditions was tested with a range of Michael acceptors and benzaldehyde and with a range of electrophiles and ethyl acrylate. The origin of the rate acceleration is discussed.

Journal Article↗

PubMed2002

A robust method for detecting CHK2/RAD53 mutations in genomic DNA.

While screening for germline CHK2 mutations in cancer cases by heteroduplex CSGE, we observed that additional PCR fragments were generated from the 3' end region of the gene that includes exons 11-14. Direct sequencing of these fragments suggested that homologous loci (possibly pseudogenes) were concomitantly being amplified. Searches of public sequence databases showed that a number of areas of the genome show a high degree of homology to exons 10-14 of the CHK2 gene. The presence of these homologous regions means that standard screening methods for detecting mutations in CHK2, based on PCR of genomic DNA, are prone to error. To circumvent this problem, we have developed a strategy, based on long-range PCR, to screen the functional copy of CHK2. Using this approach it is possible to carry out a comprehensive mutational analysis of CHK2 from genomic DNA.

Base Sequence↗

PubMed2002

Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability.

BACKGROUND & AIMS: Current models of colorectal adenoma to carcinoma progression do not fully reflect the genetic heterogeneity and complexity of the disease. The aim of the present study was to identify genetic changes discriminating adenomas that have progressed to carcinoma from adenomas that have not progressed, and to refine the current genetic models of colorectal adenoma to carcinoma progression, based on a genome-wide analysis of chromosomal aberrations. METHODS: Sixty-six nonprogressed colorectal adenomas, 46 progressed adenomas (malignant polyps), and 36 colorectal carcinomas were screened for chromosomal aberrations by comparative genomic hybridization, and for mutations in the adenomatous polyposis coli (APC) and K-ras gene. Data analysis focused on cancer-associated genetic changes in adenomas. RESULTS: Accumulation of losses in 8p21-pter, 15q11-q21, 17p12-13, and 18q12-21, and gains in 8q23-qter, 13q14-31, and 20q13 were strongly associated with adenoma-to-carcinoma progression, independent of the degree of dysplasia. Hierarchic cluster analysis demonstrated the presence of 3 distinct subgroups of adenomas, characterized by unique combinations of genetic aberrations in the adenomas (17p loss and K-ras mutation, 8q and 13q gain, and 18q loss and 20q gain, respectively). CONCLUSIONS: The presence of 2 or more of the aforementioned 7 chromosomal changes was associated with progressed colorectal adenomas and colorectal cancer. In addition, evidence was found that these chromosomal abnormalities occurred in specific combinations of a few abnormalities rather than as a mere accumulation of events, indicating the existence of multiple independent chromosomal instability pathways of colorectal cancer progression.

Adenoma↗