Evaluation of the onset time and intubation conditions of rocuronium bromide in children

Publisher's copy made available with the permission of the publisher © 1997 Australian Society of AnaesthetistsWe have assessed, in children aged three to eight years, the intubating conditions after administration of rocuronium 0.6 mg/kg at 50 or 60 seconds, in groups of 15 patients. Intubating conditions were excellent in 11, good in 3 and fair in 1 patient at 50 seconds and excellent in 12 and good in 3 patients at 60 seconds. The mean onset time, for all patients, to when the first twitch of the train of four (T1), measured at the adductor pollicis, was depressed to less than 30% and 5% of control was 50 (SD 11.4) seconds and 94 (SD 31.7) seconds respectively. Depression of T1 to less than 30% of control, measured at the adductor pollicis in children, appears to indicate that intubating conditions will be clinically acceptable when using rocuronium.P.F. McDonald, D.A. Sainsbury, R.J. Lain

Doing good qualitative research in public health: not as easy as it looks.

In this paper, we discuss qualitative research for public health professionals. Quality matters in qualitative research, but the principles by which it is judged are critically different from those used to judge epidemiology. Compared to quantitative research, good quality qualitative studies serve different aims, answer distinct research questions and have their own logic for sampling, data collection and analysis. There is, however, no need for antagonism between qualitative research and epidemiology; the two are complementary. With theoretical and methodological guidance from experienced qualitative researchers, public health professionals can learn how to make the most of qualitative research for themselves

Structural basis of transcription initiation by RNA polymerase II.

Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter

Structure and function of the initially transcribing RNA polymerase II–TFIIB complex

The general transcription factor (TF) IIB is required for RNA polymerase (Pol) II initiation and extends with its B-reader element into the Pol II active centre cleft. Low-resolution structures of the Pol II– TFIIB complex1,2 indicated how TFIIB functions in DNA recruitment, but they lacked nucleic acids and half of the B-reader, leaving other TFIIB functions3,4 enigmatic. Here we report crystal structures of the Pol II–TFIIB complex from the yeast Saccharomyces cerevisiae at 3.4A˚ resolution and of an initially transcribing complex that additionally contains theDNAtemplate and a 6-nucleotide RNAproduct.The structures reveal the entire B-reader and protein– nucleic acid interactions, and together with functional data lead to a more complete understanding of transcription initiation. TFIIB partially closes the polymerase cleft to position DNA and assist in its opening. The B-reader does not reach the active site but binds the DNA template strand upstream to assist in the recognition of the initiator sequence and in positioning the transcription start site. TFIIB rearranges active-site residues, induces binding of the catalytic metal ion B, and stimulates initial RNA synthesis allosterically. TFIIB then prevents the emergingDNA–RNAhybrid duplex from tilting, which would impair RNA synthesis. When the RNA grows beyond 6 nucleotides, it is separated from DNA and is directed to its exit tunnel by the B-reader loop. Once the RNA grows to 12–13 nucleotides, it clashes with TFIIB, triggering TFIIB displacement and elongation complex formation. Similar mechanisms may underlie all cellular transcription because all eukaryotic and archaeal RNA polymerases use TFIIB-like factors5, and the bacterial initiation factor sigma has TFIIB-like topology1,2 and contains the loop region 3.2 that resembles the B-reader loop in location, charge and function6–8. TFIIB and its counterparts may thus account for the two fundamental properties that distinguish RNA from DNA polymerases: primer-independent chain initiation and product separation from the template

Public health ethics: informing better public health practice (peer reviewed editorial)

Public health ethics has emerged and grown as an independent discipline over the last decade. It involves using ethical theory and empirical analyses to determine and justify the right thing to do in public health. In this paper, we distinguish public health ethics from clinical ethics, research ethics, public health law and politics. We then discuss issues in public health ethics including: how to weigh up the benefits, harms and costs of intervening; how to ensure that public health interventions produce fair outcomes; the potential for public health to undermine or promote the rights of citizens; and the significance of being transparent and inclusive in public health interventions. We conclude that the explicit and systematic consideration of ethical issues will, and should, become central to every public health worker’s daily practice

Public health ethics: informing better public health practice (peer reviewed editorial)

Public health ethics has emerged and grown as an independent discipline over the last decade. It involves using ethical theory and empirical analyses to determine and justify the right thing to do in public health. In this paper, we distinguish public health ethics from clinical ethics, research ethics, public health law and politics. We then discuss issues in public health ethics including: how to weigh up the benefits, harms and costs of intervening; how to ensure that public health interventions produce fair outcomes; the potential for public health to undermine or promote the rights of citizens; and the significance of being transparent and inclusive in public health interventions. We conclude that the explicit and systematic consideration of ethical issues will, and should, become central to every public health worker’s daily practice

Refusing to Endorse. A must Explanation for Pejoratives.

In her analysis of pejoratives, Eva Picardi rejects a too sharp separation between descriptive and expressive content. I reconstruct some of her arguments, endorsing Eva’s criticism of Williamson’s analysis of Dummett and developing a suggestion by Manuel Garcia Carpintero on a speech act analysis of pejoratives. Eva’s main concern is accounting for our instinctive refusal to endorse an assertion containing pejoratives because it suggests a picture of reality we do not share. Her stance might be further developed claiming that uses of pejoratives not only suggest, but also promote a wrong picture of reality. Our refusal to endorse implies rejecting not only a wrong picture of reality but also a call for participation to what that picture promotes

The Ten Essential Shared Capabilities: a framework for mental health practice

The 10 Essential Shared Capabilities (ESC) are a description of the core aspects of practice that support effective implementation and delivery of mental health care. The ESC have been derived directly from work with users, carers and mental health personnel. To support their introduction a learning pack was developed giving examples of the 10 ESC as they relate to current practice. A pilot programme across England was developed to test the acceptability and potential utility of these materials and this paper reports on the evaluation of that pilot programme. Facilitators (n=75) and learners (n=579) were asked to rate each of the seven modules contained in the learning pack. A number of recommendations have been made to improve the materials that are being acted upon

Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer.

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno-cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was > 7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node-negative patients (P = 0.04) and was similar in EGFR-positive and negative patients. In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence

Combining high-resolution cryo-electron microscopy and mutagenesis to develop cowpea mosaic virus for bionanotechnology

Particles of cowpea mosaic virus (CPMV) have enjoyed considerable success as nanoparticles. The development of a system for producing empty virus-like particles (eVLPs) of the virus, which are non-infectious and have the potential to be loaded with heterologous material, has increased the number of possible applications for CPMV-based particles. However, for this potential to be realised, it was essential to demonstrate that eVLPs were accurate surrogates for natural virus particles, and this information was provided by high-resolution cryo-EM studies of eVLPs. This demonstration has enabled the approaches developed for the production of modified particles developed with natural CPMV particles to be applied to eVLPs. Furthermore, a combination of cryo-EM and mutagenic studies allowed the development of particles which are permeable but which could still assemble efficiently. These particles were shown to be loadable with cobalt, indicating that they can, indeed, be used as nano-containers