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In 2011, there was a large measles outbreak in Dublin. Nationally 285 cases were notified to the end of December 2011, and 250 (88%) were located in the Dublin region. After the first case was notified in week 6, numbers gradually increased, with 25 notified in June and a peak of 53 cases in August. Following public health intervention including a measles-mumps-rubella (MMR) vaccination campaign, no cases were reported in the Dublin region in December 2011. Most cases (82%) were children aged between 6 months and 14 years, and 46 cases (18%) were under 12 months-old. This is the first outbreak in Dublin to utilise a geographic information system for plotting measles cases on a digital map in real time. This approach, in combination with the analysis of case notifications, assisted the department of public health in demonstrating the extent of the outbreak. The digital mapping documented the evolution of two distinct clusters of 87 (35%) cases. These measles cases were infected with genotype D4-Manchester recently associated with large outbreaks across Europe. The two clusters occurred in socio-economically disadvantaged areas and were attributable to inadequate measles vaccination coverage due in part to the interruption of a school-based MMR2 vaccination programme.

Objective: Surgery, ionising radiation and anaesthesia in the presence of an undetected pregnancy could be harmful. British guidelines state that female patients of 'childbearing age' should have their pregnancy status established before surgery. Approaching this topic with an adolescent girl can be challenging., Design: The authors conducted an observational study and a survey in their institution and a national survey of Association of Paediatric Anaesthetists (APA) linkmen., Setting: Local: Southampton. National: UK., Results: Both surveys demonstrate widespread concerns about inconsistent and informal practices. Only 45% of respondents in the authors' institution stated they ask adolescent girls if they could be pregnant. 40% of APA linkmen were unaware of national guidelines., Conclusions: This work illustrates the need for consistent national guidance. We propose that all girls who have reached menarche should be routinely offered a urine pregnancy test before any procedure under general anaesthesia.

Aim: To describe the avoidable factors associated with child deaths identified by a confidential enquiry., Method: In the Centre for Maternal and Child Enquiries confidential enquiry, a sample (13%) of cases was subjected to case note review by multidisciplinary panels attempting to identify avoidable factors associated with the deaths. Cases were selected blindly but in equal numbers from predetermined age bands and participating regions. The anonymised records were reviewed in regions remote to where the child lived and died. Panel composition, conduct and reporting were standardised., Results: 119 of 126 cases reviewed by enquiry panels had sufficient information to determine avoidable factors. These cases were comparable with the whole dataset in terms of sex and causes of death. 31 (26%) of 119 had avoidable factors that were predominantly related to individuals or agencies with a direct responsibility to the child. 51 (43%) of 119 were defined as potentially avoidable. In all, 130 factors were considered in relation to these 82 cases, and 64% of the factors were healthcare related. Avoidable factors were more likely where life-limiting illness was not present. Recurring avoidable factors included failure to recognise serious illness at the point of presentation and death occurring in children who had been lost to follow-up., Conclusion: Child Death Overview Panels now have the responsibility to review child deaths using similar methods but relying upon data forms rather than the case record. Analysis of contributory factors on a national scale has the potential to improve understanding of why children die and indicate strategies to reduce child mortality.

Aim: To validate a descriptive tool for the causes of child death, which was designed to circumvent problems posed by the analysis of a confidential enquiry., Method: 3 participants from different healthcare backgrounds used clinical data, including the entries on the medical certificate of the cause of death, to classify the root cause of 783 deaths from the Confidential Enquiry into Maternal and Child Health child death review. A bespoke hierarchical system was used. Unanimity of allocation within categories and inter-rater and intra-rater agreement were assessed. Two methods for treating disagreements were compared by assessing their effect upon the apparent incidence of different causes of death., Results: The participants were most consistent in grouping deaths due to trauma, malignancy and sudden infant death. Each was highly consistent in allocating cases to groups (κ 0.85-0.99), but the agreement between participants, although "good", was worse (κ 0.66-0.78). The greatest number of discrepancies was between diseases identified as congenital by the doctor and as chronic medical conditions by others. The method for treating disagreement between participants does not affect the commonest cause of death (trauma) but alters the ranking of the subordinate causes., Conclusion: Agreement within diagnostic categories might be improved by greater training of assessors in the use of the technique. This level of performance compares well with that of other coding systems upon their target groups.

Evidence for a functional role for extracellular matrix (ECM) proteins in adipose tissue is demonstrated in dynamic changes in expression of ECM genes during adipocyte differentiation and in obesity. Components of the ECM may regulate adipose cell number expansion by restricting pre-adipocyte proliferation, regulating apoptosis and inhibiting adipogenesis. Although pre-adipocytes express multiple proteoglycans, their role in pre-adipocyte proliferation up to now has remained unknown. The study described here was conducted to characterize roles of small leucine-rich proteoglycans (SLRPs) in adipocyte proliferation. Pre-adipocytes were seeded on plates coated with biglycan and decorin and were allowed to differentiate. In addition, pre-adipocytes were incubated on plates coated with biglycan, decorin, or fibronectin and measurements were made of cell proliferation and apoptosis. We are able to report that SLRPs decorin and biglycan did not affect differentiation of our 3T3-L1 cells; however, biglycan and decorin did reduce proliferation of pre-adipocytes, partly by induction of apoptosis. Furthermore, anti-proliferative capabilities of decorin and biglycan were nullified with removal of GAG side-chains suggesting that the chains played key roles in anti-proliferative effects of the SLRPs. We also found that co-treatment of decorin or biglycan with the proteoglycan fibronectin restored normal proliferation, an indication that multiple ECM proteins may act in concert to regulate overall proliferation rates of pre-adipocytes. These studies indicate that SLRPs may compose a regulatory factor in adipose tissue expansion, through hyperplasia., (© 2011 Blackwell Publishing Ltd.)

Nursing is associated with high levels of emotional strain and heavy workloads. Changing working conditions raise the importance of investigating job satisfaction, stress and burnout and its consequences for nurses. The aim of the study was to investigate whether work-related behaviour and experience patterns are associated with mental and physical health status in nurses. A sample of 356 nurses in four German hospitals were interviewed using questionnaires regarding work-related behaviour and experience patterns, work stress, depression, anxiety and physical symptoms ('Work-related Behaviour and Experience Pattern'--AVEM and ERI). The main result of this study is that unhealthy work-related behaviour and experience patterns (i.e. the excessive ambitious type and the resigned type) are associated with reduced mental and physical health. Preventive, as well as intervention, strategies are needed that focus both on the individual as well as on working conditions., (© 2011 Blackwell Publishing.)

A search for a very-high-energy (VHE; ≥100  GeV) γ-ray signal from self-annihilating particle dark matter (DM) is performed towards a region of projected distance r∼45-150  pc from the Galactic center. The background-subtracted γ-ray spectrum measured with the High Energy Stereoscopic System (H.E.S.S.) γ-ray instrument in the energy range between 300 GeV and 30 TeV shows no hint of a residual γ-ray flux. Assuming conventional Navarro-Frenk-White and Einasto density profiles, limits are derived on the velocity-weighted annihilation cross section (σv) as a function of the DM particle mass. These are among the best reported so far for this energy range and in particular differ only little between the chosen density profile parametrizations. In particular, for the DM particle mass of ∼1  TeV, values for (σv) above 3×10(-25)  cm(3) s(-1) are excluded for the Einasto density profile.

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

The work presented herein was completed in an effort to characterize the forces influencing ventilation in gravity sewers and to develop a mathematical model, based on conservation of momentum, capable of accounting for friction at the headspace/pipe interface, drag at the air/water interface, and buoyancy caused by air density differences between a sewer headspace and ambient. Experiments were completed on two full scale sewer reaches in Australia. A carbon monoxide-based tracer technique was used to measure the ventilation rate within the sewer headspaces. Additionally, measurements of pressure, relative humidity, and temperature were measured in the ambient air and sewer headspace. The first location was a five kilometre long sewer outfall beginning at a wastewater treatment plant and terminating at the ocean. The second location was a large gravity sewer reach fitted with ventilation fans. At the first location the headspace was entirely sealed except for openings that were controlled during the experiments. In this situation forces acting on the headspace air manifested mostly as a pressure distribution within the reach, effectively eliminating friction at the pipe wall. At the second location, air was forced to move near the same velocity as the wastewater, effectively eliminating drag at the air/water interface. These experiments allowed individual terms of the momentum equation to be evaluated. Experimental results were compared to the proposed mathematical model. Conclusions regarding model accuracy are provided along with model application guidance and assumptions.

Background: Nosocomial diarrhoea is common and its investigation carries a significant healthcare cost. This study aimed to determine the utility of faecal lactoferrin (FL), a readily measurable marker of intestinal inflammation, in hospitalized patients with diarrhoea., Methods: FL was quantified in consecutive faecal samples submitted to a hospital pathology laboratory. Patient data were extracted from hospital records. Receiver-operator curve (ROC) analysis was performed in a subset of patients where a decision about low or high likelihood of inflammation could be confidently made. Multivariate analyses were performed to identify associations with an elevated FL. Cost analyses were also performed., Results: A total of 511 faecal samples from 433 patients (48% male, median age 67 years) was studied. Median FL concentration was 3.4 µg/mL (range 0-288). ROC analysis indicated an optimal cut-off value of 1.25 µg/mL (sensitivity 92%, specificity 97%, negative predictive value 97%) compared with the manufacturer's cut-off of 7.25 µg/mL (60%, 66% and 85% respectively). Multivariate analysis at the lower cut-off minimized potentially confounding variables. Proton pump inhibitor use independently increased (OR 2.3, 95% CI 1.5-3.8) and current smoking reduced (0.61, 0.38-0.99) the likelihood of an elevated FL. Only one out of 32 bacteriological positive samples would have been missed if FL was instituted as a screening test prior to microbiological assessment, which could have reduced laboratory-related costs by up to 56%., Conclusion: In hospitalized patients, a normal FL effectively excludes inflammatory diarrhoea and is proposed as a screening test prior to microbiological assessment of faeces. Prospective evaluation of this approach is warranted., (© 2010 The Authors. Internal Medicine Journal © 2010 Royal Australasian College of Physicians.)

Aims/hypothesis: Up-regulation of the receptor for AGEs (RAGE) and its ligands in diabetes has been observed in various tissues. Here, we sought to determine levels of RAGE and one of its most important ligands, S100B, in diabetic retina, and to investigate the regulatory role of S100B and RAGE in Müller glia., Methods: Streptozotocin-diabetes was induced in Sprague-Dawley rats. RAGE, S100B and glial fibrillary acidic protein (GFAP) were detected in retinal cryosections. In parallel, the human retinal Müller cell line, MIO-M1, was maintained in normal glucose (5.5 mmol/l) or high glucose (25 mmol/l). RAGE knockdown was achieved using small interfering RNA (siRNA), while soluble RAGE was used as a competitive inhibitor of RAGE ligand binding. RAGE, S100B and cytokines were detected using quantitative RT-PCR, western blotting, cytokine protein arrays or ELISA. Activation of mitogen-activated protein kinase (MAPK) by RAGE was determined by western blotting., Results: Compared with non-diabetic controls, RAGE and S100B were significantly elevated in the diabetic retina with apparent localisation in the Müller glia, occurring concomitantly with upregulation of GFAP. Exposure of MIO-M1 cells to high glucose induced increased production of RAGE and S100B. RAGE signalling via MAPK pathway was linked to cytokine production. Blockade of RAGE prevented cytokine responses induced by high glucose and S100B in Müller glia., Conclusions/interpretation: Hyperglycaemia in vivo and in vitro exposure to high glucose induce upregulation of RAGE and its ligands, leading to RAGE signalling, which links to pro-inflammatory responses by retinal Müller glia. These data shed light on the potential clinical application of RAGE blockade to inhibit the progression of diabetic retinopathy.

In July 2008, office workers in Dublin complained of influenza-like illness preceding and interspersing two cases of notified Legionnaires' disease. Legionella pneumophila serogroup 1 was identified in both cooling towers supplying the office. A retrospective cohort study was undertaken to investigate possible Pontiac fever (PF). Forty-seven employees (23%) met the clinical case definition for PF but confirmatory testing was negative. Exposure to the smoking area situated beside the cooling towers was associated with an increased risk of PF (RR 2.4, 95% CI 1.5-3.8). The diagnosis of PF should be considered when many persons exposed to a possible reservoir of Legionella spp. present with flu-like symptoms. More sensitive microbiological tests would allow better confirmation and more comprehensive reporting of PF. Early detection is vital to prevent potentially severe illness and outbreaks of PF or Legionnaires' disease.

Objective: To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital., Design: Randomised controlled trial., Setting: Community covered by four primary care trusts, England., Participants: 204 adults aged more than 60 living at home or in residential care who had fallen and called an emergency ambulance but were not taken to hospital., Interventions: Referral to community fall prevention services or standard medical and social care., Main Outcome Measures: The primary outcome was the rate of falls over 12 months, ascertained from monthly diaries. Secondary outcomes were scores on the Barthel index, Nottingham extended activities of daily living scale, and falls efficacy scale at baseline and by postal questionnaire at 12 months. Analysis was by intention to treat., Results: 102 people were allocated to each group. 99 (97%) participants in the intervention group received the intervention. Falls diaries were analysed for 88.6 person years in the intervention group and 84.5 person years in the control group. The incidence rates of falls per year were 3.46 in the intervention group and 7.68 in the control group (incidence rate ratio 0.45, 95% confidence interval 0.35 to 0.58, P<0.001). The intervention group achieved higher scores on the Barthel index and Nottingham extended activities of daily living and lower scores on the falls efficacy scale (all P<0.05) at the 12 month follow-up. The number of times an emergency ambulance was called because of a fall was significantly different during follow-up (incidence rate ratio 0.60, 95% confidence interval 0.40 to 0.92, P=0.018)., Conclusion: A service to prevent falls in the community reduced the fall rate and improved clinical outcome in the high risk group of older people who call an emergency ambulance after a fall but are not taken to hospital., Trial Registration: Current Controlled Trials ISRCTN67535605.

Introduction: The appropriate management of asymptomatic congenital cystic adenomatoid malformations of the lung (CCAM) remains controversial. The aim of this study is to determine the outcome of expectant management of these lesions and the sensitivity of antenatal ultrasound diagnosis., Material and Methods: A retrospective review was undertaken of all cases identified from prospectively collected databases with an antenatal or postnatal diagnosis of CCAM in the Northern region of England between 1985 and 2006 where such lesions underwent resection only when symptomatic., Results: Thirty-seven cases of confirmed CCAM were identified antenatally or postnatally. Twenty-six (70%) were identified by antenatal ultrasound scans (during a period of near-universal antenatal scanning), of whom 21 (81%) were liveborn. In total, 16 of 29 (55%) liveborn infants with CCAM were symptomatic, and either died within the first postnatal week or underwent resection. Thirteen (45% of livebirths) were managed expectantly and remained asymptomatic. The sensitivity of antenatal ultrasound screening for CCAM increased over the period to 90% in the latter half of the study (p=0.035), although the positive predictive value (66%) did not improve., Conclusions: Expectant management was a reasonable option for almost half of the babies, but over one third required surgery for CCAM, most becoming symptomatic in infancy. In view of the uncertainty that surrounds decisions regarding expectant or pre-emptive resection in asymptomatic infants, the authors advocate having an open and honest discussion when counselling parents (particularly antenatally) regarding surveillance or expectant management as a reasonable strategy.

For the purpose of patient dose audit, clinical audit and radiology workload analysis, data from Radiology Information Systems (RIS) at many hospitals are collected using a database and the analysis was automated using a statistical package and Visual Basic coding. The database is a Structured Query Language database, which can be queried using an off-the-shelf statistical package, Statistica. Macros were created to automatically format the data to a consistent format between different hospitals ready for analysis. These macros can also be used to automate further analysis such as detailing mean kV, mAs and entrance surface dose per room and per gender. Standard deviation and standard error of the mean are also generated. Graphs can also be generated to illustrate the trends in doses between different variables such as room and gender. Collectively, this information can be used to generate a report. A process that once could take up to 1 d to complete now takes around 1 h. A major benefit in providing the service to hospital trusts is that less resource is now required to report on RIS data, making the possibility of continuous dose audit more likely. Time that was spent on sorting through data can now be spent on improving the analysis to provide benefit to the customer. Using data sets from RIS is a good way to perform dose audits as the huge numbers of data available provide the bases for very accurate analysis. Using macros written in Statistica Visual Basic has helped sort and consistently analyse these data. Being able to analyse by exposure factors has provided a more detailed report to the customer.

In this case series we present a variety of different cardiac toxicities with 5-fluorouracil and its pro-drug capecitabine, including myocardial infarction, cardiomyopathy, sinoatrial and atrioventricular node dysfunction, takotsubo cardiomyopathy and QT prolongation with torsade-de pointes ventricular tachycardia. We stress the fact that while vasospasm is a well-recognized side-effect of this class of chemotherapeutic agent, broader cardiotoxicity is commonly seen and an increased awareness of the range of toxicity is necessary if repeat toxicity is to be avoided.

Practical and philosophical aspects of radiation protection in diagnostic radiology have changed very little over the past 50 y even though patient doses have continued to rise significantly in this period. This rise has been driven by technological developments, such as multi-slice computed tomography, that have been able to improve diagnostic accuracy but not necessarily provide the same level of risk-benefit to all patients or groups of patients given the dose levels involved. Can practical radiation protection strategies hope to keep abreast of these ongoing developments? A project was started in 1992 in Liverpool that aimed to develop IT driven quality assurance (QA)/radiation protection software tools based upon a modular quality assurance dose data system. One of the modules involved the assessment of the patient entrance surface air kerma (ESAK) for an X-ray examination that was based upon the use of calibrated X-ray tube exposure factors to calculate ESAK as well as collecting appropriate patient details (age, sex, weight, thickness etc). The package also contained modules for logging all necessary equipment performance QA data. This paper will outline the experience gained with this system through its transition from a local application on a stand alone PC within the department to the current web-based approach. Advantages of a web-based approach to delivering such an application as well as centrally storing data originating on many hospital sites will be discussed together with the scientific support processes that can be developed with such a system. This will include local, national and international considerations. The advantages of importing radiographic examination details directly from other electronic storage systems such as a hospital's radiology information system will be presented together with practical outcomes already achieved. This will include the application of statistical techniques to the very large data sets generated. The development of new examination QA performance indicators will be discussed. The application of web-based IT tools for QA and radiation protection in diagnostic radiology is already opening up the possibility of developing new and improved scientific support services as well as research possibilities in radiological informatics. These will be outlined together with areas for possible future development by the medical physics community.

High blood pressure (BP) and elevated homocysteine are reported as independent risk factors for CVD and stroke in particular. The main genetic determinant of homocysteine concentrations is homozygosity (TT genotype) for the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, typically found in approximately 10% of Western populations. The B-vitamins folate, vitamin B12 and vitamin B6 are the main nutritional determinants of homocysteine, with riboflavin more recently identified as a potent modulator specifically in individuals with the TT genotype. Although observational studies have reported associations between homocysteine and BP, B-vitamin intervention studies have shown little or no BP response despite decreases in homocysteine. Such studies, however, have not considered the MTHFR C677T polymorphism, which has been shown to be associated with BP. It has been shown for the first time that riboflavin is an important determinant of BP specifically in individuals with the TT genotype. Research generally suggests that 24 h ambulatory BP monitoring provides a more accurate measure of BP than casual measurements and its use in future studies may also provide important insights into the relationship between the MTHFR polymorphism and BP. Further research is also required to investigate the association between specific B-vitamins and BP in individuals with different MTHFR genotypes in order to confirm whether any genetic predisposition to hypertension is correctable by B-vitamin intervention. The present review will investigate the evidence linking the MTHFR C677T polymorphism to BP and the potential modulating role of B-vitamins.

In June and July 2008, two office workers were admitted to a Dublin hospital with Legionnaires' disease. Investigations showed that cooling towers in the basement car park were the most likely source of infection. However, positive results from cooling tower samples by polymerase chain reaction (PCR) did not correlate with subsequent culture results. Also, many employees reported Pontiac fever-like morbidity following notification of the second case of Legionnaires' disease. In total, 54 employees attended their general practitioner or emergency department with symptoms of Legionnaires' disease or Pontiac fever. However, all laboratory tests for Legionnaires' disease or Pontiac fever were negative. In this investigation, email was used extensively for active case finding and provision of time information to employees and medical colleagues. We recommend clarification of the role of PCR in the diagnosis of legionellosis and also advocate for a specific laboratory test for the diagnosis of the milder form of legionellosis as in Pontiac fever.

The present guidelines aim to provide comprehensive information regarding the laboratory diagnosis of infections caused by Chlamydia trachomatis in East European countries. These recommendations contain important information for laboratory staff working with sexually transmitted infections (STIs) and/or STI-related issues. Individual East European countries may be required to make minor national adjustments to these guidelines as a result of lack of accessibility to some reagents or equipment, or laws in a specific country.

Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of approximately 10(15) electron volts. We report the detection of gamma rays--tracers of such cosmic rays--from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H.E.S.S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.

Background: In normal healthy individuals, the level of tissue factor (TF) expression on monocytes is low. However, studies have shown that patients with cardiovascular disease (CVD) have elevated levels of TF. As the risk of CVD increases with age and is more prominent in the male population, it is postulated that TF expression may be positively correlated with these factors. However, very few studies have examined the relationship between age and gender on TF expression., Methods: This study evaluated the influence of age and gender on TF expression using data obtained from female (n = 44) and male (n = 27) subjects. We also examined the influence of BMI and total fat intake on TF expression in the same subjects., Results: The results of our study found no significant difference in TF expression between the male and female subgroups. No correlation was found between TF and age, BMI or total fat intake in the male or female groupings., Conclusion: It may be postulated that the risk of CVD development in such populations may not be due to increases in TF expression with increasing age or gender differences.

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

In November and December 2008, six cases of suspect wound botulism were reported in heroin injecting drug users, all residents in Dublin, Ireland. Patients were aged between 23-42 years of age; four cases were male; one patient died shortly after admission. The patients presented to four different hospitals across the city. Botulism in injecting drug users in Ireland was last reported in 2002.

The quality and accessibility of anaesthesia-related information available to patients on the Internet is a growing concern for the specialty. We sought to evaluate the quality of anaesthesia-related websites using a simple scoring system. The scoring system comprised quality and technical scores individually, and these were also combined into a total score. Test-retest reliability was assessed by calculating intraclass correlation coefficients. We employed the four most popular search engines and one meta-search engine, using the search term "general anaesthesia". Only the first 10 sites retrieved were scored. The intraclass correlation coefficients for all terms demonstrated at least moderate agreement and the total scores demonstrated high consistency r = 0.852, 0.774 (P < 0.001, and P < 0.003 respectively). There were 18 duplicate websites and 32 were scored. There was no difference between search engines for any of the three scores awarded. The majority of websites were rated as either 'poor' or fair' across all scores. Our study indicates that quality anaesthesia-related information is unlikely to be retrieved by patients using the Internet.

The very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon or satellite based instruments in the detection of very-high-energy (>600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.

In the past few decades, several models have predicted an energy dependence of the speed of light in the context of quantum gravity. For cosmological sources such as active galaxies, this minuscule effect can add up to measurable photon-energy dependent time lags. In this Letter a search for such time lags during the High Energy Stereoscopic System observations of the exceptional very high energy flare of the active galaxy PKS 2155-304 on 28 July 2006 is presented. Since no significant time lag is found, lower limits on the energy scale of speed of light modifications are derived.

Objective: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR)., Methods: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007)., Results: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue., Conclusions: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Introduction: Pruritus ani is a common condition with many causes, predominately anorectal pathology. There are some new insights and therapies, but the most recommendations are based on low-level evidence., Patients and Methods: A literature search was carried out using Medline and the internet with the keywords 'pruritus ani' from 1950 to 2007., Results: A review of the evidence is presented and a management plan based on the elimination of irritants and scratching, general control measures and active treatment measures is offered., Conclusions: Treatment of primary and secondary pruritus ani has a good prospect of regression of symptoms and skin changes.

In recent years, mental health services across Europe have undergone major organizational change with a move from institutional to community care. In such a context, the impact of change on the job satisfaction of psychiatric nurses has received little attention in the literature. This paper reports on the job satisfaction of psychiatric nurses and data were collected in 2003. The population of qualified psychiatric nurses (n = 800) working in a defined geographical health board area was surveyed. Methodological triangulation with a between-methods approach was used in the study. Data were collected on job satisfaction using a questionnaire adopted from the Occupational Stress Indicator. A response rate of 346 (43%) was obtained. Focus groups were used to collect qualitative data. Factors influencing levels of job satisfaction predominantly related to the nurses work location. Other factors influencing job satisfaction included choice of work location, work routine, off duty/staff allocation arrangements, teamwork and working environment. The results of the study highlight to employers of psychiatric nurses the importance of work location, including the value of facilitating staff with choices in their working environment, which may influence the recruitment and retention of nurses in mental health services.

In the clinical/microbiological laboratory there are currently several ways of separating specific cells from a fluid suspension. Conventionally cells can be separated based on size, density, electrical charge, light-scattering properties, and antigenic surface properties. Separating cells using these parameters can require complex technologies and specialist equipment. This paper proposes new Bio-MEMS (microelectromechanical systems) filtration chips manufactured using deep reactive ion etching (DRIE) technology that, when used in conjunction with an optical microscope and a syringe, can filter and grade cells for size without the requirement for additional expensive equipment. These chips also offer great versatility in terms of design and their low cost allows them to be disposable, eliminating sample contamination. The pumping mechanism, unlike many other current filtration techniques, leaves samples mechanically and chemically undamaged. In this paper the principles behind harnessing passive pumping are explored, modelled, and validated against empirical data, and their integration into a microfluidic device to separate cells from a mixed population suspension is described. The design, means of manufacture, and results from preliminary tests are also presented.

Background: There is no consensus on the usage of erythropoietin in the immediate postoperative period to prevent anemia and delayed graft function., Methods: A retrospective case note audit of renal transplants included hemoglobin (Hb) and serum creatinine (Scr) values preoperatively as well as at days 7, 14, 30, 60, and 90. Patients were categorized as those receiving erythropoietin during the first 6 months posttransplant (Epo+ve) and those not receiving any erythropoietin (Epo-ve)., Results: Hb decreased from 12.4 +/- 1.6 g/L preoperatively to 9.5 +/- 1.5 g/L at day 14 and then rose to 10.5 +/- 1.6 g/L at 1 month and 12.4 +/- 1.7 g/L at 3 months. There was no difference in absolute Hb values in three transplant groups. Scr decreased from 597.0 +/- 200.1 mmol/L preoperatively to 254.1 +/- 196.9 mmol/L at day 14 and continued to fall to 163.8 +/- 98.9 mmol/L at 1 month and 147.8 +/- 66.9 mmol/L at 3 months. There was no difference in absolute Hb values and delayed graft function in the three transplant groups., Conclusion: With respect to anemia and delayed graft function, the use of erythropoietin in the first 3 months had little impact. We suggest that such an expensive medication may be safely omitted in the immediate postoperative period.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

In May 2000, public health authorities in Dublin, Ireland, identified a cluster of unexplained severe illness among injecting drug users (IDUs). Similar clusters were also reported in Scotland and England. Concurrent investigations were undertaken to identify the aetiology and source of the illnesses. In Dublin, 22 IDUs were identified with injection-site inflammation resulting in hospitalization or death; eight (36%) died. Common clinical findings among patients with severe systemic symptoms included leukaemoid reaction and cardiogenic shock. Seventeen (77%) patients reported injecting heroin intramuscularly in the 2 weeks before illness. Of 11 patients with adequate specimens available for testing, two (18%) were positive by 16S rDNA PCR for Clostridium novyi. Clinical and laboratory findings suggested that histotoxic Clostridia caused a subset of infections in these related clusters. Empiric treatment for infections among IDUs was optimized for anaerobic organisms, and outreach led to increased enrolment in methadone treatment in Dublin. Many unique legal, medical, and public health challenges were encountered during the investigation of this outbreak.

Background: There is an increasing focus on improving the detection and management of patients with chronic kidney disease (CKD). Data on CKD prevalence based on population sampling are now available, but there are few data about CKD patients attending nephrology services or how such services are organized., Aim: To survey services for CKD patients nationally., Methods: A pre-piloted questionnaire was sent to all 72 renal units in the UK, referring to the situation in June 2004., Results: Seventy units (97%) responded. The median ratio of prevalent CKD patients/prevalent renal replacement therapy (RRT) patients in the 25 units with data was 3.7 (IQR 2.7-5.7) and the median ratio of CKD stage 4 and 5 patients/prevalent RRT patients was 0.6 (IQR 0.4-1.1). This gives an estimated 140 000 CKD patients under the care of UK nephrologists, with 23 000 at CKD stage 4 or 5 (excluding those on RRT). Very few units had a full complement of the recommended multi-skilled renal team. Counsellors and psychologist were the most common perceived shortages. Of 70 responding units, 50 (74%) were using low clearance clinics for management of advanced CKD patients. Elective dialysis access services often had long delays, with median waiting time for vascular access ranging between 1 and 36 weeks, and for Tenchkoff catheter, between 0 and 12 weeks., Discussion: CKD patients are a significant workload for UK nephrologists. Current provision of service is variable, and services need to be re-designed to cope with the expected future increase of referral of CKD patients.

Purpose: Free prostate specific antigen, complexed PSA and human glandular kallikrein 2 have independently been tested against the gold standard of total PSA for prostate cancer screening in largely white populations. With the incidence of prostate cancer much higher in black men, we sought to evaluate these markers simultaneously in a predominantly black population., Materials and Methods: A total of 138 men, of whom 108 were black, underwent ultrasound guided biopsy of the prostate for tPSA levels greater than 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn before biopsy and analyzed for tPSA, fPSA, cPSA and hK2 concentrations using standard methods (hK2 assay is for research use only, not for use in diagnostic procedures). The areas under the receiver operator characteristic curves were determined for each marker as well as biomarker combinations. Additionally, each parameter's specificity, positive and negative predictive values, and theoretical screening efficiency were assessed at or above the 95% sensitivity level., Results: A total of 43 (31.1%) men had prostate cancer by biopsy. While the AUC for %fPSA was statistically the highest (0.822, p <0.001), cPSA offered the highest specificity (31.6%) and positive predictive power (31.7%) of any of the tested biomarkers at comparable sensitivity (greater than 95%). The calculated efficiency of cPSA (51.4%) was also higher than the other markers. Nearly 20% of biopsies would be avoided using cPSA vs standard tPSA screening methods., Conclusions: Comparing the major PSA isoforms and hK2, cPSA alone appears to offer superior diagnostic discrimination for cancer detection in a predominantly black population.

In 2004, an outbreak of hepatitis A occurred in European tourists returning from Egypt. The reported hepatitis A attack rates varied considerably between tourists from different European countries. To determine the reason for this divergence in attack rates, a survey was undertaken with the following objectives: (a) documentation of national hepatitis A prevention policies for people travelling to Egypt and (b) documentation of hepatitis A reporting practices in these countries. A questionnaire was compiled and distributed to 13 European countries. All eight of the countries that responded had produced guidelines for the prevention of travel-associated hepatitis A. Between 2001-2003, 40% (range 4-51) of hepatitis A cases reported annually were associated with travel abroad. This occurred despite the fact that all countries recommended active vaccination with hepatitis A vaccine for people travelling to Egypt for holidays. There was no standard case definition for reporting confirmed cases in the countries that reported hepatitis A cases. As it is likely that travel-associated infections will increase as more people take overseas holidays, innovative ways to increase the number of travellers who seek and adhere to appropriate medical advice prior to travel must be explored. In addition, we recommend the use of the European Commission case definition for notification of confirmed cases of hepatitis A.

The theoretical impacts of anthropogenic habitat degradation on genetic resources have been well articulated. Here we use a simulation approach to assess the magnitude of expected genetic change, and review 31 studies of 23 neotropical tree species to assess whether empirical case studies conform to theory. Major differences in the sensitivity of measures to detect the genetic health of degraded populations were obvious. Most studies employing genetic diversity (nine out of 13) found no significant consequences, yet most that assessed progeny inbreeding (six out of eight), reproductive output (seven out of 10) and fitness (all six) highlighted significant impacts. These observations are in line with theory, where inbreeding is observed immediately following impact, but genetic diversity is lost slowly over subsequent generations, which for trees may take decades. Studies also highlight the ecological, not just genetic, consequences of habitat degradation that can cause reduced seed set and progeny fitness. Unexpectedly, two studies examining pollen flow using paternity analysis highlight an extensive network of gene flow at smaller spatial scales (less than 10 km). Gene flow can thus mitigate against loss of genetic diversity and assist in long-term population viability, even in degraded landscapes. Unfortunately, the surveyed studies were too few and heterogeneous to examine concepts of population size thresholds and genetic resilience in relation to life history. Future suggested research priorities include undertaking integrated studies on a range of species in the same landscapes; better documentation of the extent and duration of impact; and most importantly, combining neutral marker, pollination dynamics, ecological consequences, and progeny fitness assessment within single studies.

It is well known that the greatest risk for mortality post-renal transplant is cardiovascular death. We compared a modified cardiac risk assessment system among renal transplant patients who subsequently died versus the group that survived. There was a good correlation between the low, medium, and high scores with survival. The deceased group had significantly greater cardiovascular scores than case controls.

A simple cardiovascular risk score used in our center to plan cardiovascular workup for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher risk group, with a score of >12 out of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with an relative rate of graft loss within 60 days of >4 (P = .053). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.