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Matthew Davies

Publications and source records attributed to Matthew Davies.

5 recordsLinked to original sources
PubMed2007

Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase.

Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with low nanomolar binding affinities were identified that bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate. These compounds also prevented growth of cultured parasites at low micromolar concentrations. Models that suggest the mode of inhibitor binding is based on shape complementarity, matching hydrophobic regions of inhibitor and enzyme, and interaction of inhibitors with amino acid residues F188, H185, and R265 are supported by mutagenesis data. These results further highlight PfDHODH as a promising new target for chemotherapeutic intervention in prevention of malaria and provide better understanding of the factors that determine specificity over human dihydroorotate dehydrogenase.

Aminobiphenyl Compounds↗
PubMed2005

Assessment of resident surgical skills: is testing feasible?

OBJECTIVE: We have previously shown that in a single residency program objective structured assessment of technical skills (OSATS) is a reliable and valid method of assessing surgical competency. Our goal was to establish feasibility of this evaluation instrument when administered at multiple residency programs throughout the US, and assess the impact of a laboratory-based surgical curriculum on results. STUDY DESIGN: An OSATS exam was administered to 116 residents from 5 residency programs. One of the residency programs had participated in a comprehensive surgical curriculum over a 4-year period of time. The exam consisted of 3 open and 3 laparoscopic tasks. Residents were graded by both a blinded and unblinded examiner with task-specific checklist, global rating scale, pass/fail assessment, and tasks were timed. All tasks were performed on life-like models. RESULTS: Examinations were successfully completed at all sites. Each exam required 90 minutes of resident time. Reliability indices calculated with Cronbach's alpha were .97 for overall global rating and .95 for checklists. Interrater reliability between blinded and unblinded examiners ranged from .71 to .97 for individual tasks and was .95 overall. Assessment of construct validity (the ability to distinguish among residency levels) found significant differences among the residents for both blinded and unblinded examiners for all evaluation outcomes except time. For the test overall, the global rating scale showed significant differences among all 4 residency levels. The checklist showed significant differences at three levels (PGY3-4 >PGY2 >PGY1). Approximate cost for replaceable items was 40 US dollars to 150 per resident depending on which tasks were chosen. Comparison of scores between residents who received a laboratory-based curriculum and those who did not revealed significantly higher scores and shorter time to complete tasks for the group who received additional training. CONCLUSION: Large-scale testing has confirmed that OSATS is an objective, reliable, and valid method to assess surgical skills, and can easily be administered in most residency programs. A laboratory-based surgical curriculum improved test results and reduced time to complete tasks.

Clinical Competence↗
PubMedDate not supplied

Towards a consensus on datasets and evaluation metrics for developing B-cell epitope prediction tools.

A B-cell epitope is the three-dimensional structure within an antigen that can be bound to the variable region of an antibody. The prediction of B-cell epitopes is highly desirable for various immunological applications, but has presented a set of unique challenges to the bioinformatics and immunology communities. Improving the accuracy of B-cell epitope prediction methods depends on a community consensus on the data and metrics utilized to develop and evaluate such tools. A workshop, sponsored by the National Institute of Allergy and Infectious Disease (NIAID), was recently held in Washington, DC to discuss the current state of the B-cell epitope prediction field. Many of the currently available tools were surveyed and a set of recommendations was devised to facilitate improvements in the currently existing tools and to expedite future tool development. An underlying theme of the recommendations put forth by the panel is increased collaboration among research groups. By developing common datasets, standardized data formats, and the means with which to consolidate information, we hope to greatly enhance the development of B-cell epitope prediction tools.

Animals↗
PubMedDate not supplied

The impact of health professionals' attitudes about being registered donors on the availability of organs.

The mismatch between supply and demand in organ donation is well documented. Although there are many reasons for this mismatch, failure of health professionals to identify potential donors or to gain consent from bereaved relatives is considered to be significant. Such failures may be due to the attitudes of health professionals themselves towards becoming organ donors. This study focuses on the level of commitment shown by health care professionals and their student equivalents to organ donation, and assesses the ways in which they identify themselves as potential organ donors. These findings are evaluated and suggestions for future practice are offered.

Adolescent↗