Presenting patient data in the electronic care record: the role of timelines.

OBJECTIVE: To establish the current level of awareness and investigate the use of timelines within clinical computing systems as an organized display of the electronic patient record (EPR). DESIGN: Multicentre survey conducted using questionnaires and interview. SETTING: Seven UK hospitals and several general practice surgeries. PARTICIPANTS: A total of 120 healthcare professionals completed a questionnaire which directed structured interviews. Participants fell into two cohorts according to whether or not they had used clinical timelines, which gave 60 'timeline users' and 60 'prospective timeline users'. MAIN OUTCOME MEASURES: To investigate the awareness of timelines, and the potential benefits of timelines within clinical computing systems. RESULTS: Fifty-eight percent of participants had not heard of the specific term 'timelines' despite 75% of users utilizing a form of timeline on a daily basis. The potential benefits of future timelines were clinical audit (95%CI 77.6-91.6), increased time efficiency (95%CI 77.7-91.6%), reduced clinical error (95%CI 71.0-86.7) and improved patient safety (95%CI 70.0-85.9). One continuous timeline view between primary and secondary care was considered to be of great potential benefit in allowing communication via a unified patient record. CONCLUSIONS: The concept of timelines has enjoyed proven success in healthcare in the USA and in other sectors worldwide. Clinicians are supportive of timelines in healthcare. Formal input from clinicians should be sought when designing and implementing computer systems in healthcare. Timelines in healthcare support clinicians' cognitive processes by improving the amount of data available and improving the way in which data are presented.

Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate transcription.

The presence of Set2-mediated methylation of H3K36 (K36me) correlates with transcription frequency throughout the yeast genome. K36me targets the Rpd3S complex to deacetylate transcribed regions and suppress cryptic transcription initiation at certain genes. Here, using a genome-wide approach, we report that the Set2-Rpd3S pathway is generally required for controlling acetylation at coding regions. When using acetylation as a functional readout for this pathway, we discovered that longer genes and, surprisingly, genes transcribed at lower frequency exhibit a stronger dependency. Moreover, a systematic screen using high-resolution tiling microarrays allowed us to identify a group of genes that rely on Set2-Rpd3S to suppress spurious transcripts. Interestingly, most of these genes are within the group that depend on the same pathway to maintain a hypoacetylated state at coding regions. These data highlight the importance of using the functional readout of histone codes to define the roles of specific pathways.

Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin.

Nucleosomes must be deacetylated behind elongating RNA polymerase II to prevent cryptic initiation of transcription within the coding region. RNA polymerase II signals for deacetylation through the methylation of histone H3 lysine 36 (H3K36), which provides the recruitment signal for the Rpd3S histone deacetylase complex (HDAC). The recognition of methyl H3K36 by Rpd3S requires the chromodomain of its Eaf3 subunit. Paradoxically, Eaf3 is also a subunit of the NuA4 acetyltransferase complex, yet NuA4 does not recognize methyl H3K36 nucleosomes. In Saccharomyces cerevisiae, we found that methyl H3K36 nucleosome recognition by Rpd3S also requires the plant homeobox domain (PHD) of its Rco1 subunit. Thus, the coupled chromo and PHD domains of Rpd3S specify recognition of the methyl H3K36 mark, demonstrating the first combinatorial domain requirement within a protein complex to read a specific histone code.

Chromatin marks and machines, the missing nucleosome is a theme: gene regulation up and downstream.

A remarkable insight to emerge from chromatin immunoprecipitation studies is that the steps leading to chromatin remodeling and preinitiation complex (PIC) assembly differ significantly, depending upon the gene and its biological context (Cosma, 2002). However, when multiple systems are compared, the differences illuminate checkpoints and generalities that provide insights into the most salient features of mechanism. This concept dominated presentations at the 2004 Chromatin and Transcription by RNA Polymerase II meeting held at the Lake Tahoe Granlibakken Conference Center.