Clinical review: Mass casualty triage – pandemic influenza and critical care

Worst case scenarios for pandemic influenza planning in the US involve over 700,000 patients requiring mechanical ventilation. UK planning predicts a 231% occupancy of current level 3 (intensive care unit) bed capacity. Critical care planners need to recognise that mortality is likely to be high and the risk to healthcare workers significant. Contingency planning should, therefore, be multi-faceted, involving a robust health command structure, the facility to expand critical care provision in terms of space, equipment and staff and cohorting of affected patients in the early stages. It should also be recognised that despite this expansion of critical care, demand will exceed supply and a process for triage needs to be developed that is valid, reproducible, transparent and consistent with distributive justice. We advocate the development and validation of physiological scores for use as a triage tool, coupled with candid public discussion of the process

FAD Mutations in Amyloid Precursor Protein Do Not Directly Perturb Intracellular Calcium Homeostasis

Disturbances in intracellular calcium homeostasis are likely prominent and causative factors leading to neuronal cell death in Alzheimer's disease (AD). Familial AD (FAD) is early-onset and exhibits autosomal dominant inheritance. FAD-linked mutations have been found in the genes encoding the presenilins and amyloid precursor protein (APP). Several studies have shown that mutated presenilin proteins can directly affect calcium release from intracellular stores independently of Aβ production. Although less well established, there is also evidence that APP may directly modulate intracellular calcium homeostasis. Here, we directly examined whether overexpression of FAD-linked APP mutants alters intracellular calcium dynamics. In contrast to previous studies, we found that overexpression of mutant APP has no effects on basal cytosolic calcium, ER calcium store size or agonist-induced calcium release and subsequent entry. Thus, we conclude that mutated APP associated with FAD has no direct effect on intracellular calcium homeostasis independently of Aβ production

EEG responses to standardised noxious stimulation during clinical anaesthesia: a pilot study.

BACKGROUND During clinical anaesthesia, the administration of analgesics mostly relies on empirical knowledge and observation of the patient's reactions to noxious stimuli. Previous studies in healthy volunteers under controlled conditions revealed EEG activity in response to standardised nociceptive stimuli even at high doses of remifentanil and propofol. This pilot study aims to investigate the feasibility of using these standardised nociceptive stimuli in routine clinical practice. METHODS We studied 17 patients undergoing orthopaedic trauma surgery under general anaesthesia. We evaluated if the EEG could track standardised noxious phase-locked electrical stimulation and tetanic stimulation, a time-locked surrogate for incisional pain, before, during, and after the induction of general anaesthesia. Subsequently, we analysed the effect of tetanic stimulation on the surgical pleth index as a peripheral, vegetative, nociceptive marker. RESULTS We found that the phase-locked evoked potentials after noxious electrical stimulation vanished after the administration of propofol, but not at low concentrations of remifentanil. After noxious tetanic stimulation under general anaesthesia, there were no consistent spectral changes in the EEG, but the vegetative response in the surgical pleth index was statistically significant (Hedges' g effect size 0.32 [95% confidence interval 0.12-0.77], P=0.035). CONCLUSION Our standardised nociceptive stimuli are not optimised for obtaining consistent EEG responses in patients during clinical anaesthesia. To validate and sufficiently reproduce EEG-based standardised stimulation as a marker for nociception in clinical anaesthesia, other pain models or stimulation settings might be required to transfer preclinical studies into clinical practice. CLINICAL TRIAL REGISTRATION DRKS00017829

Evolution in the black hole mass-bulge mass relation: a theoretical perspective

We explore the growth of super-massive black holes and host galaxy bulges in the galaxy population using the Millennium Run LCDM simulation coupled with a model of galaxy formation. We find that, if galaxy mergers are the primary drivers for both bulge and black hole growth, then in the simplest picture one should expect the mBH-mbulge relation to evolve with redshift, with a larger black hole mass associated with a given bulge mass at earlier times relative to the present day. This result is independent of an evolving cold gas fraction in the galaxy population. The evolution arises from the disruption of galactic disks during mergers that make a larger fractional mass contribution to bulges at low redshift than at earlier epochs. There is no comparable growth mode for the black hole population. Thus, this effect produces evolution in the mBH-mbulge relation that is driven by bulge mass growth and not by black holes.Comment: 6 pages, 3 figures, minor revisions, replaced with accepted MNRAS versio

Psychosocial care for persons affected by emergencies and major incidents: a Delphi study to determine the needs of professional first responders for education, training and support

Background The role of ambulance clinicians in providing psychosocial care in major incidents and emergencies is recognised in recent Department of Health guidance. The study described in this paper identified NHS professional first responders’ needs for education about survivors’ psychosocial responses, training in psychosocial skills, and continuing support. Method Ambulance staff participated in an online Delphi questionnaire, comprising 74 items (Round 1) on 7-point Likert scales. Second-round and third-round participants each received feedback based on the previous round, and responded to modified versions of the original items and to new items for clarification. Results One hundred and two participants took part in Round 1; 47 statements (64%) achieved consensus. In Round 2, 72 people from Round 1 participated; 15 out of 39 statements (38%) achieved consensus. In Round 3, 49 people from Round 2 participated; 15 out of 27 statements (59%) achieved consensus. Overall, there was consensus in the following areas: ‘psychosocial needs of patients’ (consensus in 34/37 items); ‘possible sources of stress in your work’ (8/9); ‘impacts of distress in your work’ (7/10); ‘meeting your own emotional needs’ (4/5); ‘support within your organisation’ (2/5); ‘needs for training in psychosocial skills for patients’ (15/15); ‘my needs for psychosocial training and support’ (5/6). Conclusions Ambulance clinicians recognise their own education needs and the importance of their being offered psychosocial training and support. The authors recommend that, in order to meet patients’ psychosocial needs effectively, ambulance clinicians are provided with education and training in a number of skills and their own psychosocial support should be enhanced

Philosophy with children : facilitating children's voices on childhood

Increasingly there is a search for participatory research methods that work to ensure children’s authentic voices are heard. In this presentation we will propose that Philosophy with Children might be employed as a research method that facilitates children’s participation and voice in research. Further, it may also impact positively in children’s wider participation and engagement in recognising children’s agency and conceptual autonomy. We will discuss the advantages of using philosophical dialogue as a method for collecting data and will also consider challenges that arise from using Philosophy with Children as a research tool. In discussing the challenges and opportunities afforded by such a method, the presentation will draw on two studies to exemplify the approach. One study explored what kind of society children want to live in, and the second is an on-going international study that aims to explore children’s conceptions of child/childhood. We will also suggest that using Philosophy with Children might be considered as addressing the need for rights-based approaches to research as in affording children ownership of the dialogue it does not assume children as deficient in their capacities and it recognises children’s particular perspectives on the world. In addition, we will suggest that using a philosophical approach to gathering children’s views might offer a deeper insight into their thinking of and understanding about the world. Elements of the approaches used in the study will be discussed in order to gauge the strengths and limitations of using practical philosophy as a means of gathering data in subsequent analysis. In juxtaposition to the Philosophy with Children approach discussed, we will comment briefly on the use of an alternative research method, Nominal Group Technique, which was also used in the first project. In comparing the two approaches we aim to show where Philosophy with Children may provide richer and deeper evidence when seeking children’s views. While the presentation will not share the findings of either of the projects mentioned above, the approach taken in using Philosophy with Children as a research method, relates strongly to the findings of the initial project and the goals of the Children’s Voices on Childhood project. In using Philosophy with Children, it will be proposed that, while there may be some limitations in using the approach, it takes account of children’s voices in research; it affords opportunities to explore children’s conceptual thinking and the application to ‘real life’; it allows children to have ownership of the topic under consideration; and it potentially leads to addressing children’s status in wider society

Accelerated discharge of patients in the event of a major incident: observational study of a teaching hospital

BACKGROUND: Since October 2002 in the UK Primary Care Trusts (PCTs) have had statutory responsibility for having and maintaining a Major Incident plan and since 2005 they have been obliged to co-operate with other responders to an incident. We aimed to establish the number of beds in our Trust which could be freed up over set periods of time in the event of a major incident and the nature and quantity of support which might be required from PCTs in order to achieve this. METHODS: Repeated survey over 12 days in 3 months of hospital bed occupancy by type of condition and discharge capacity in an 855-bed UK tertiary teaching hospital also providing secondary care services. Outcome measures were bed spaces which could be generated, timescale over which this could happen and level and type of PCT support which would be required to achieve this. RESULTS: Mean beds available were 78 immediately, a further 69 in 1–4 hours and a further 155 in 4–12 hours, generating a total of 302 beds (36% of hospital capacity) within 12 hours of an incident. This would require support from a PCT of 150,000 population of 10 nursing care beds, 20 therapy-supported intermediate care beds, and 25 care packages in patients' own homes. CONCLUSION: In order to fulfill the requirements of the Civil Contingencies Act 2004, PCTs should plan to have surge capacity in the order of 30 residential placements and 25 community support packages per 150,000 population to support Acute Trusts in the event of a major incident

Antibody production in micro-organisms

Global demand for monoclonal antibody-based therapeutics (Mab’s) far exceeds current production capacity, and is expected to continue to grow based on current development pipelines. Despite their proven efficacy in a large number of indications, equitable use of these drugs is limited by the high cost of CHO-cell based production and purification. Micro-organisms such as yeasts and filamentous fungi present an attractive alternative for antibody production, but will require extensive genetic modification to achieve both high titers and mammalian-like glycosylation patterns in a secreted product that is easily purified. Towards this end, we developed state-of-the-art genetic engineering tools for eight micro-organisms to enable the highly efficient, targeted multiplexed integrations necessary for antibody production in these hosts. We demonstrated successful antibody production in several of these micro-organisms, paving the way to low-cost microbial fermentation to replace CHO fermentation

Preparedness of emergency departments in northwest England for managing chemical incidents: a structured interview survey

<p>Abstract</p> <p>Background</p> <p>A number of significant chemical incidents occur in the UK each year and may require Emergency Departments (EDs) to receive and manage contaminated casualties. Previously UK EDs have been found to be under-prepared for this, but since October 2005 acute hospital Trusts have had a statutory responsibility to maintain decontamination capacity. We aimed to evaluate the level of preparedness of Emergency Departments in North West England for managing chemical incidents.</p> <p>Methods</p> <p>A face-to-face semi-structured interview was carried out with the Nurse Manager or a nominated deputy in all 18 Emergency Departments in the Region.</p> <p>Results</p> <p>16/18 departments had a written chemical incident plan but only 7 had the plan available at interview. All had a designated decontamination area but only 11 felt that they were adequately equipped. 12/18 had a current training programme for chemical incident management and 3 had no staff trained in decontamination. 13/18 could contain contaminated water from casualty decontamination and 6 could provide shelter for casualties before decontamination.</p> <p>Conclusion</p> <p>We have identified major inconsistencies in the preparedness of North West Emergency Departments for managing chemical incidents. Nationally recognized standards on incident planning, facilities, equipment and procedures need to be agreed and implemented with adequate resources. Issues of environmental safety and patient dignity and comfort should also be addressed.</p

SHARC-II 350 micron Observations of Thermal Emission from Warm Dust in z>=5 Quasars

We present observations of four z>= SDSS quasars at 350 micron with the SHARC-II bolometer camera on the Caltech Submillimeter Observatory. These are among the deepest observations that have been made by SHARC-II at 350 micron, and three quasars are detected at >=3 sigma significance, greatly increasing the sample of 350 micron (corresponds to rest frame wavelengths of <60 micron at z>=5), detected high-redshift quasars. The derived rest frame far-infrared (FIR) emission in the three detected sources is about five to ten times stronger than that expected from the average SED of the local quasars given the same 1450A luminosity. Combining the previous submillimeter and millimeter observations at longer wavelengths, the temperatures of the FIR-emitting warm dust from the three quasar detections are estimated to be in the range of 39 to 52 K. Additionally, the FIR-to-radio SEDs of the three 350 micron detections are consistent with the emission from typical star forming galaxies. The FIR luminosities are ~10^{13} L_solar and the dust masses are >= 10^{8}M_solar. These results confirm that huge amounts of warm dust can exist in the host galaxies of optically bright quasars as early as z~6. The universe is so young at these epochs (~1 Gyr) that a rapid dust formation mechanism is required. We estimate the size of the FIR dust emission region to be about a few kpc, and further provide a comparison of the SEDs among different kinds of dust emitting sources to investigate the dominant dust heating mechanism.Comment: 15 pages, 3 figures, accepted for publication in A