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A story, a chemical mystery of the Sherlock Holmes genre, is related, with a break at which students and others may consider a solution. After they have done so, they can read to the end and find out what Holmes and Watson said to one another. Emphasis is on qualitative analysis, blood tests, and properties of biological substances.

Bacterial cytokinesis is driven by the septal ring apparatus, the assembly of which in Escherichia coli is directed to mid-cell by the Min system. Despite suffering aberrant divisions at the poles, cells lacking the minCDE operon (Min–) have an almost normal growth rate. We developed a generally applicable screening method for synthetic lethality in E. coli, and used it to select for transposon mutations ( slm) that are synthetically lethal (or sick) in combination with Δ minCDE. One of the slm insertions mapped to envC ( yibP), proposed to encode a lysostaphin-like, metallo-endopeptidase that is exported to the periplasm by the general secretory (Sec) pathway. Min– EnvC– cells showed a severe division defect, supporting a role for EnvC in septal ring function. Accordingly, we show that an EnvC–green fluorescent protein fusion, when directed to the periplasm via the twin-arginine export system, is both functional and part of the septal ring apparatus. Using an in-gel assay, we also present evidence that EnvC possesses murein hydrolytic activity. Our results suggest that EnvC plays a direct role in septal murein cleavage to allow outer membrane constriction and daughter cell separation. By uncovering genetic interactions, the synthetic lethal screen described here provides an attractive new tool for studying gene function in E. coli. [ABSTRACT FROM AUTHOR]

A response by I. A. Walker and colleagues to a letter to the editor regarding their article "Global oximetry: an international anaesthesia quality improvement project," is presented.

Effective locomotion in nature happens by transitioning across multiple modes (e.g., walk, run, climb). Despite this, far more mechanistic understanding of terrestrial locomotion has been on how to generate and stabilize around near-steady-state movement in a single mode. We still know little about how locomotor transitions emerge from physical interaction with complex terrain. Consequently, robots largely rely on geometric maps to avoid obstacles, not traverse them. Recent studies revealed that locomotor transitions in complex three-dimensional (3D) terrain occur probabilistically via multiple pathways. Here, we show that an energy landscape approach elucidates the underlying physical principles. We discovered that locomotor transitions of animals and robots self-propelled through complex 3D terrain correspond to barrier-crossing transitions on a potential energy landscape. Locomotor modes are attracted to landscape basins separated by potential energy barriers. Kinetic energy fluctuation from oscillatory self-propulsion helps the system stochastically escape from one basin and reach another to make transitions. Escape is more likely toward lower barrier direction. These principles are surprisingly similar to those of near-equilibrium, microscopic systems. Analogous to free-energy landscapes for multipathway protein folding transitions, our energy landscape approach from first principles is the beginning of a statistical physics theory of multipathway locomotor transitions in complex terrain. This will not only help understand how the organization of animal behavior emerges from multiscale interactions between their neural and mechanical systems and the physical environment, but also guide robot design, control, and planning over the large, intractable locomotor-terrain parameter space to generate robust locomotor transitions through the real world., Competing Interests: The authors declare no competing interest.

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Background: The Royal College of Anaesthetists audited consultant supervision and responsibility in anaesthesia in the UK during 2003., Methods: Consultants (supervising) and non-consultants (supervised) were surveyed on their attitudes to supervision, experience of their own hospital system for supervision and of induction for new starters. Local coordination was achieved through anaesthesia audit coordinators who provided information on local policies, induction programmes and anaesthesia charts. Supervision was audited over a 5-day period., Results: 135 departments of anaesthesia took part (43% of 315 departments), questionnaires being returned by 2297 anaesthetists. Anaesthesia record charts in use do not meet criteria considered desirable locally. Most trainees, but less than half staff grade/associate specialists, received an induction programme, often not supported by written documentation. Consultants find conflicting demands of service and supervision difficult. Many work in systems which do not permit providing direct, immediate support to those supervised. Most anaesthetists think supervision is very important. Around half disagree with national guidance that every NHS patient should have a named consultant. Two per cent of non-consultants during the audit period reported assistance from consultants not being obtainable soon enough., Conclusions: This audit found departure from standards and the potential for risk and failure. New standards may be needed regarding anaesthesia record sheets, induction, accountability, when to seek help and care of sick patients. Supervision systems in over 40% of hospitals need review to ensure they provide a named consultant and immediate direct support for elective lists.

Background: Information on anaesthesia interventions, plans and risks is needed by patients and carers alike and is a key component of the Good Practice In Consent initiative. Existing information materials may under-represent what patients are able to contribute., Method: UK anaesthetic departments were surveyed on provision of written patient information. The response rate was 66% (177/267)., Results: Fifty-five per cent of respondents reported providing patient information materials for planned surgical admission, mainly on general anaesthesia, regional analgesia and pain. A minority provided information for children and for critical care patients. Few (32%) had sought feedback from patients, and few used existing sources of guidance. Most (85%) wanted improvements, with a four-to-one majority favouring central resources developed by The Royal College of Anaesthetists., Conclusions: Working in parallel does not give our hospitals excellent, effective patient information materials. Demand exists for The Royal College of Anaesthetists to lead in this area. Working in partnership with patients and taking into account existing written guidance is important but has often been overlooked.

Aim: The aim of this study is to investigate patients' perceptions and experiences of chronic pain management before and after attending pain services., Method: A sample of 245 patients with chronic pain, who attended specialist pain services in 11 UK hospitals, were interviewed using a structured questionnaire. Patients' ages ranged between 23 and 86 years (median 51 years), and the duration of pain ranged between six months and 57 years (median five years)., Results: Patients reported that pain had had a profound effect on their lives, restricting daily living and leisure activities. 33 per cent (81) were classified as medically disabled. Patients' perceptions and attitudes to the management of chronic pain varied. Their main concern was that, although they wanted a specific diagnosis, they were often not given a reason for their chronic pain., Conclusion: Pain management requires a significant amount of input by health professionals. Patients wanted advice on the best techniques to help them cope with chronic pain. Most patients had previously tried many different pain treatments to obtain short-term pain relief. One third of patients had waited up to four months for their initial pain assessment at the pain service. Once referred to specialist pain services, patients were satisfied with their care. Almost half (47 per cent, 115) of the interviewees reported that their pain had improved. As chronic pain has a profound effect on patients' lives, it is important that early diagnosis, treatment and referral to appropriate specialists is given high priority. This study has raised the awareness and understanding of an important, but often misunderstood area.

Background: This article describes the use of focus groups in research, including the advantages and disadvantages of using this type of research methodology. Using an example of a focus group of patients who experienced chronic pain, the authors discuss the planning, organisation, conduct and analysis of focus groups., Conclusion: Focus groups enabled an exploration of the topics in-depth including obtaining insight from a patient's perspective of the management of their chronic pain. It was important and of value to take into account the experiences and expectations of health service delivery from a consumer's perspective.

The relevance of social relationships to the phenomena of depression among the aged was examined. The study was based on the reduced reinforcement hypothesis which predicts a low rate of social relationships (i.e. the loss of positive reinforcement) for those individuals who are prone to depression. This hypothesis was both tested and confirmed among the residents in homes for the aged in Berlin. The senior citizens who reported a low rate of social activities had higher depression scores than those reporting a higher rate of such social involvement. These results were confirmed for various indicators of social participation. A further variable influencing the rate of depression was identified as the self-rating of personal health. The results are discussed within both a behavioral and a cognitive framework.