An observational study of critical care physicians' assessment and decision-making practices in response to patient referrals.

Previous studies of critical care admissions have largely compared patients that have been granted or declined admission. To better understand the decision process itself, our ethnographic approach combined observation of and interviews with critical care physicians in a large English hospital. We observed 30 critical care doctors managing 71 referrals and conducted ten interviews with senior decision-makers to explore the themes raised by our observations. We analysed data using the constant comparative method. We found that the decision to move a patient to critical care was just one way in which the trajectory of critical illness could be modified. When patients were admitted to critical care, it was not always for invasive monitoring or advanced organ support, with some admitted for more general medical and/or nursing care. When patients were declined admission, they were not simply forgotten or left behind; they nevertheless underwent careful assessment and follow-up. Thus, depicting admission or refusal as a binary event is misleading. We suggest that prescriptive admission algorithms are problematic for clinicians, in that they may not take into account the complexity of clinical practice.

Opening up the black box: an introduction to qualitative research methods in anaesthesia.

Qualitative research methods are a group of techniques designed to allow the researcher to understand phenomena in their natural setting. A wide range is used, including focus groups, interviews, observation, and discourse analysis techniques, which may be used within research approaches such as grounded theory or ethnography. Qualitative studies in the anaesthetic setting have been used to define excellence in anaesthesia, explore the reasons behind drug errors, investigate the acquisition of expertise and examine incentives for hand-hygiene in the operating theatre. Understanding how and why people act the way they do is essential for the advancement of anaesthetic practice, and rigorous, well-designed qualitative research can generate useful data and important insights. Meticulous social scientific methods, transparency, reproducibility and reflexivity are markers of quality in qualitative research. Tools such as the consolidated criteria for reporting qualitative research checklist and the critical appraisal skills programme are available to help authors, reviewers and readers unfamiliar with qualitative research assess its merits.

A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease.

The study of de novo point mutations (new germline mutations arising from the gametes of the parents) remained largely static until the arrival of next-generation sequencing technologies, which made both whole-exome sequencing (WES) and whole-genome sequencing (WGS) feasible in practical terms. Single nucleotide polymorphism genotyping arrays have been used to identify de novo copy-number variants in a number of common neurodevelopmental conditions such as schizophrenia and autism. By contrast, as point mutations and microlesions occurring de novo are refractory to analysis by these microarray-based methods, little was known about either their frequency or impact upon neurodevelopmental disease, until the advent of WES. De novo point mutations have recently been implicated in schizophrenia, autism and mental retardation through the WES of case-parent trios. Taken together, these findings strengthen the hypothesis that the occurrence of de novo mutations could account for the high prevalence of such diseases that are associated with a marked reduction in fecundity. De novo point mutations are also known to be responsible for many sporadic cases of rare dominant mendelian disorders such as Kabuki syndrome, Schinzel-Giedion syndrome and Bohring-Opitz syndrome. These disorders share a common feature in that they are all characterized by intellectual disability. In summary, recent WES studies of neurodevelopmental and neuropsychiatric disease have provided new insights into the role of de novo mutations in these disorders. Our knowledge of de novo mutations is likely to be further accelerated by WGS. However, the collection of case-parent trios will be a prerequisite for such studies. This review aims to discuss recent developments in the study of de novo mutations made possible by technological advances in DNA sequencing.

Direct estimation of the mutation rate at dinucleotide microsatellite loci in Arabidopsis thaliana (Brassicaceae).

The mutation rate at 54 perfect (uninterrupted) dinucleotide microsatellite loci is estimated by direct genotyping of 96 Arabidopsis thaliana mutation accumulation lines. The estimated rate differs significantly among motif types with the highest rate for AT repeats (2.03 x 10(-3) per allele per generation), intermediate for CT (3.31 x 10(-4)), and lowest for CA (4.96 x 10(-5)). The average mutation rate per generation for this sample of loci is 8.87 x 10(-4) (s.e.=2.57 x 10(-4)). There is a strong effect of initial repeat number, particularly for AT repeats, with mutation rate increasing with the length of the microsatellite locus in the progenitor line. Controlling for motif and initial repeat number, chromosome 4 exhibited an elevated mutation rate relative to other chromosomes. The great majority of mutations were gains or losses of a single repeat. Generally, the data are consistent with the stepwise mutation model of microsatellite evolution. Several lines exhibited multiple step changes from the progenitor sequence, but it is unclear whether these are multi-step mutations or multiple single-step mutations. A survey of dinucleotide repeats across the entire Arabidopsis genome indicates that AT repeats are most abundant, followed by CT, and CA.

Interprofessional handover and patient safety in anaesthesia: observational study of handovers in the recovery room.

BACKGROUND: We aimed to describe how anaesthetists hand over information and professional responsibility to nurses in the operating theatre recovery room. METHODS: We carried out non-participant practice observation and in-depth interviews with practitioners working in the recovery room of an English hospital and used qualitative methods to analyse the resulting transcripts. RESULTS: We observed 45 handovers taking place between 17 anaesthetists and 15 nurses in the recovery room of the operating theatre suite. These took place in an environment that is event-driven, time-pressured, and prone to concurrent distractions. Anaesthetists and nurses often had differing expectations of the content and timing of information transfer. The point at which transfer of responsibility for the patient occurred during the handover process was variable and depended not only on the condition of the patient but also on the professional relationship between the nurse and doctor concerned. Handover also provided an 'audit point' in care where the patient's intraoperative progress was reviewed and plans were made for further management. Here, as in the transfer of responsibility, we found evidence that nurses play a greater role in defining the limits of anaesthetists' practice than might be expected. CONCLUSIONS: Patient handovers in the recovery room are largely informal, but nevertheless show many inherent tensions, both professional and organizational. Although formalized handover procedures are often advocated for the promotion of safety, we suggest that they are likely to work best when the informal elements, and the cultural factors underlying them, are acknowledged.

What defines expertise in regional anaesthesia? An observational analysis of practice.

BACKGROUND: Published work on knowledge in regional anaesthesia has focused on competence, for instance by identifying numbers of procedures required to achieve competence, or by defining criteria for successful performance of blocks. We aimed to define expertise in regional anaesthesia and examine how it is acquired. METHODS: We observed anaesthetists performing 15 regional anaesthetic blocks and analysed the resulting transcripts qualitatively and in detail. RESULTS: Expertise in regional anaesthesia encompasses technical fluency but also includes non-cognitive skills such as handling of the patient (communicating, anticipating and minimizing discomfort) and recognizing the limits of safe practice (particularly deciding when to stop trying to insert a block). Such elements may be underplayed by the experts who possess them. Focusing on a small number of regional anaesthetic procedures in detail (as is standard with such qualitative analytical approaches) has also allowed us to develop a model for the acquisition of expertise. In this model, trainees learn how to balance theoretical and practical knowledge by reflection on their clinical experiences, an iterative process which leads to the embedding of knowledge in the expert's personal repertoire of individual techniques. CONCLUSIONS: Expertise in regional anaesthesia extends beyond competence at technical performance; non-cognitive elements are also vital. Further work is needed to test our learning model, and the hypothesis that learning can be enhanced by deliberate promotion of the tacit elements of 'expertise' we have described.

Adverse events in anaesthetic practice: qualitative study of definition, discussion and reporting.

BACKGROUND: This study aimed to explore how critical and acceptable practice are defined in anaesthesia and how this influences the discussion and reporting of adverse incidents. Method. We conducted workplace observations of, and interviews with, anaesthetists and anaesthetic staff. Transcripts were analysed qualitatively for recurrent themes and quantitatively for adverse events in anaesthetic process witnessed. We also observed departmental audit meetings and analysed meeting minutes and report forms. RESULTS: The educational value of discussing events was well-recognized; 28 events were discussed at departmental meetings, of which 5 (18%) were presented as 'critical incidents'. However, only one incident was reported formally. Our observations of anaesthetic practice revealed 103 minor events during the course of over 50 anaesthetic procedures, but none were acknowledged as offering the potential to improve safety, although some were direct violations of 'acceptable' practice. Formal reporting appears to be constrained by changing boundaries of what might be considered 'critical', by concerns of loss of control over formally reported incidents and by the perception that reporting schemes outside anaesthesia have purposes other than education. CONCLUSIONS: Despite clear official definitions of criticality in anaesthesia, there is ambiguity in how these are applied in practice. Many educationally useful events fall outside critical incident reporting schemes. Professional expertise in anaesthesia brings its own implicit safety culture but the reluctance to adopt a more explicit 'systems approach' to adverse events may impede further gains in patient safety in anaesthesia.

Making monitoring 'work': human-machine interaction and patient safety in anaesthesia.

This study aimed to explore the use of electronic monitoring within the context of anaesthetic practice. We conducted workplace observation of, and interviews with, anaesthetists and other anaesthetic staff in two UK hospitals. Transcripts were analysed inductively for recurrent themes. Whilst formal sources of knowledge in anaesthesia deal with the issue of monitoring in terms of theoretical principles and performance specifications of devices, anaesthetists in practice often 'disbelieve' monitoring information. They call on and integrate other sources of knowledge about the patient, especially from their clinical assessment. The ability to distinguish 'normal' and 'abnormal' findings is vital. Confidence in electronic information varies with experience, as does the degree to which electronic information may be considered 'redundant'. We conclude that electronic monitoring brings new dimensions of understanding but also the potential for new ways of misunderstanding. The tacit knowledge underlying the safe use of monitoring deserves greater acknowledgement in training and practice.

Expertise in practice: an ethnographic study exploring acquisition and use of knowledge in anaesthesia.

BACKGROUND: Expert professional practice in any field is known to rely on both explicit (formal) and tacit (personal) forms of knowledge. Current anaesthetic training programmes appear to favour explicit knowledge and measurable competencies. We aimed to describe and explore the way different types of knowledge are learned and used in anaesthetic practice. METHOD: Qualitative approach using non-participant observation of, and semi-structured interviews with, anaesthetic staff in two English hospitals. RESULTS: The development of expertise in anaesthesia rests on the ability to reconcile and interpret many sources of knowledge--clinical, social, electronic, and experiential--and formal theoretical learning. Experts have mastered technical skills but are also able to understand the dynamic and uncertain condition of the anaesthetized patient and respond to changes in it. This expertise is acquired by working with colleagues, and, importantly, by working independently, to develop personal routines. Routines mark the successful incorporation of new knowledge but also function as a defence against the inherent uncertainty of anaesthetic practice. The habits seen in experts' routines are preferred ways of working chosen from a larger repertoire of techniques which can also be mobilized as changing circumstances demand. CONCLUSIONS: Opportunities for developing expertise are linked to the independent development of personal routines. Evidence-based approaches to professional practice may obscure the role played by the interpretation of knowledge. We suggest that the restriction of apprenticeship-style training threatens the acquisition of anaesthetic expertise as defined in this paper.

Factors influencing the evaluation of telehealth interventions: preliminary results from a qualitative study of evaluation projects in the UK.

We have carried out a qualitative study of factors that influence the evaluation of telehealth. The study concerned six telehealth projects that are being tracked over two years. In the first 12 months of the study we carried out semistructured interviews and made observations of the participants in the projects. Each case study involved 5-15 subjects, many of whom were interviewed several times. The results indicate that important issues affecting telehealth evaluation include developing and maintaining the technology, reorganization of clinical and administrative duties, professional dynamics, and the difficulty of integrating service provision and evaluation. The findings suggest that the evaluation of telehealth interventions is highly complex, and that this complexity is often underestimated in the design and conduct of evaluation studies.

Phylogenetic relationships of the enigmatic angiosperm family Podostemaceae inferred from 18S rDNA and rbcL sequence data.

The phylogenetic relationships of some angiosperm families have remained enigmatic despite broad phylogenetic analyses of rbcL sequences. One example is the aquatic family Podostemaceae, the relationships of which have long been controversial because of major morphological modifications associated with their aquatic habit. Podostemaceae have variously been associated with Piperaceae, Nepenthaceae, Polygonaceae, Caryophyllaceae, Scrophulariaceae, Rosaceae, Crassulaceae, and Saxifragaceae. Two recent analyses of rbcL sequences suggest a possible sister-group relationship of Podostemaceae to Crassulaceae (Saxifragales). However, the branch leading to Podostemaceae was long, and use of different outgroups resulted in alternative placements. We explored the phylogenetic relationships of Podostemaceae using 18S rDNA sequences and a combined rbcL + 18S rDNA matrix representing over 250 angiosperms. In analyses based on 18S rDNA data, Podostemaceae are not characterized by a long branch; the family consistently appears as part of a Malpighiales clade that also includes Malpighiaceae, Turneraceae, Passifloraceae, Salicaceae, Euphorbiaceae, Violaceae, Linaceae, Chrysobalanaceae, Trigoniaceae, Humiriaceae, and Ochnaceae. Phylogenetic analyses based on a combined 18S rDNA + rbcL data set (223 ingroup taxa) with basal angiosperms as the outgroup also suggest that Podostemaceae are part of a Malpighiales clade. These searches swapped to completion, and the shortest trees showed enhanced resolution and increased internal support compared to those based on 18S rDNA or rbcL alone. However, when Gnetales are used as the outgroup, Podostemaceae appear with members of the nitrogen fixing clade (e.g., Elaeagnaceae, Ulmaceae, Rhamnaceae, Cannabaceae, Moraceae, and Urticaceae). None of the relationships suggested here for Podostemaceae receives strong bootstrap support. Our analyses indicate that Podostemaceae are not closely allied with Crassulaceae or with other members of the Saxifragales clade; their closest relatives, although still uncertain, appear to lie elsewhere in the rosids.

Inferring complex phylogenies using parsimony: an empirical approach using three large DNA data sets for angiosperms.

To explore the feasibility of parsimony analysis for large data sets, we conducted heuristic parsimony searches and bootstrap analyses on separate and combined DNA data sets for 190 angiosperms and three outgroups. Separate data sets of 18S rDNA (1,855 bp), rbcL (1,428 bp), and atpB (1,450 bp) sequences were combined into a single matrix 4,733 bp in length. Analyses of the combined data set show great improvements in computer run times compared to those of the separate data sets and of the data sets combined in pairs. Six searches of the 18S rDNA + rbcL + atpB data set were conducted; in all cases TBR branch swapping was completed, generally within a few days. In contrast, TBR branch swapping was not completed for any of the three separate data sets, or for the pairwise combined data sets. These results illustrate that it is possible to conduct a thorough search of tree space with large data sets, given sufficient signal. In this case, and probably most others, sufficient signal for a large number of taxa can only be obtained by combining data sets. The combined data sets also have higher internal support for clades than the separate data sets, and more clades receive bootstrap support of > or = 50% in the combined analysis than in analyses of the separate data sets. These data suggest that one solution to the computational and analytical dilemmas posed by large data sets is the addition of nucleotides, as well as taxa.

Bridging the gap between ecology and genetics: The case of freshwater zooplankton.

The large body of existing ecological data on freshwater systems has generated an exciting array of genetical and evolutionary hypotheses. In particular, freshwater zooplankton, due to their short generation times and ease of manipulation, are being actively studied. Results of these studies show strong links between the genetic structure of populations and habitat size, diapause stages, interspecific hybridization, intensity of selection, and subsequent ecological divergence of coexisting genotypes. Yet much of the data remains surprising and paradoxical, providing fuel for further experimental and molecular studies.

Dietary patterns and nutrient intakes of toddlers from low-income families in Denver, Colorado.

Over a 2-year period, dietary and socioeconomic data were collected from 793 food records of 90 toddlers, aged 1 to 2 years, who were predominantly U.S. Hispanics living in low-income households in Denver, CO. This study was part of a larger investigation designed to assess the efficacy of vitamin and mineral supplements in young children. The toddlers were randomly assigned to one of five treatment groups: multivitamin; multivitamin and iron; multivitamin, iron, and zinc; multivitamin and zinc; or placebo. Three-day food records that were collected from the toddlers at the beginning of the study, at 3 months, and at 6 months were used to assess the dietary and nutrient intakes. Meal patterns were devised on the basis of the frequency of food consumption and common food combinations. Nutrient values were calculated using a diet analyzer program. Nutrient analysis of the toddlers' diets indicated that iron and magnesium were consumed least frequently, whereas more than adequate amounts of protein (193% of the Recommended Dietary Allowance) and sodium (207% of minimum requirements for healthy persons) were consumed. No significant differences in nutrient intakes were observed among the treatment groups, suggesting that the vitamin and mineral supplements had no effect. A difference in energy intake was observed over time with the 6-month and 3-month intakes significantly higher than the initial intakes. There was also a high consumption of carbonated beverages. Despite the low income levels of the families, these toddlers were consuming adequate amounts of food; however, an educational component aimed at reducing the toddlers' high intakes of protein, sodium, and carbonated drinks may help improve the present feeding practices of the mothers.