Light bending and X-ray echoes from behind a supermassive black hole.

The innermost regions of accretion disks around black holes are strongly irradiated by X-rays that are emitted from a highly variable, compact corona, in the immediate vicinity of the black hole1-3. The X-rays that are seen reflected from the disk4, and the time delays, as variations in the X-ray emission echo or 'reverberate' off the disk5,6, provide a view of the environment just outside the event horizon. I Zwicky 1 (I Zw 1) is a nearby narrow-line Seyfert 1 galaxy7,8. Previous studies of the reverberation of X-rays from its accretion disk revealed that the corona is composed of two components: an extended, slowly varying component extending over the surface of the inner accretion disk, and a collimated core, with luminosity fluctuations propagating upwards from its base, which dominates the more rapid variability9,10. Here we report observations of X-ray flares emitted from around the supermassive black hole in I Zw 1. X-ray reflection from the accretion disk is detected through a relativistically broadened iron K line and Compton hump in the X-ray emission spectrum. Analysis of the X-ray flares reveals short flashes of photons consistent with the re-emergence of emission from behind the black hole. The energy shifts of these photons identify their origins from different parts of the disk11,12. These are photons that reverberate off the far side of the disk, and are bent around the black hole and magnified by the strong gravitational field. Observing photons bent around the black hole confirms a key prediction of general relativity.

Military health outreach on Exercise ASKARI SERPENT: a discussion of clinical and ethical challenges.

Exercise ASKARI SERPENT (Ex AS) is an annual British Army medical exercise that sees the deployment of a medical regiment to rural Kenya. The exercise involves the delivery of health outreach clinics and health education to the civilian population alongside Kenyan governmental and non-governmental organisations. This article includes a post hoc analysis of the ethical and clinical challenges that clinicians faced during Ex AS, applying a four-quadrant approach to ethical decision-making. This article intends to stimulate further debate and discussion on how to best prepare clinicians for clinical challenges and ethical decision-making on future exercises and operations. We conclude that our experiences on Ex AS can provide an insight on how to develop predeployment training for clinicians. Furthermore, the universal nature of the challenges faced on Ex AS can be applied to training for future contingency operations.

Modelling of vapour intrusion into a building impacted by a fuel spill in Antarctica.

A new vapour intrusion contaminant transport model was designed specifically to allow an assessment of the impact of a hydrocarbon fuel spill on air quality in cold region buildings. The model is applied to a recent situation in Antarctica, where a diesel spill impacted the construction of a new building. For the first time, this model allows consideration of the diffusive resistance of different vapour barrier to the transport of hydrocarbons into the building and an assessment of the effectiveness of different products. Site specific indoor air criteria are derived. Five scenarios are modelled at field temperatures: (1) build on current contaminated site; (2) excavate contaminated soil, backfill with clean soil and assess impact of residual contamination; (3) excavate and backfill with remediated (biopile) soil; (4) backfill with remediated soil and assess impact of residual contamination; (5) backfill with remediated soil and assess impact of a potential future fuel spill. Two different vapour barriers, a co-extruded ethylene vinyl alcohol (EVOH) geomembrane (VB1) and a linear low-density (LLDPE) geomembrane (VB2), are investigated for each scenario and compared to a base case with no vapour barrier, providing quantifiable evidence of the benefit of installing an engineered vapour barrier Contaminant concentrations were below regulatory limits for Scenarios (2-5) with VB1 and air exchange in the building. For all scenarios, the EVOH geomembrane (VB1) was consistently superior at reducing vapour transport into the building indoor air space over the LLDPE geomembrane (VB2) and no vapour barrier. The risk mitigation measures developed for this contaminated Antarctic site may be relevant for other buildings in cold regions.

Comment on "Water-water correlations in electrolyte solutions probed by hyper-Rayleigh scattering" [J. Chem. Phys. 147, 214505 (2017)].

The work by Shelton [J. Chem. Phys. 147, 214505 (2017)] discussed and interpreted differences with a previous study by Chen et al. [Sci. Adv. 2, e1501891 (2016)] regarding the influence of electrolytes on the structure of water. It is argued by Shelton [J. Chem. Phys. 147, 214505 (2017)] that impurities and hyper-Raman scattering contributions are the reasons for differences in the measured second harmonic intensity between the above two studies. Here, we show that these proposed effects are not relevant and discuss the influence of pulse parameters, focusing on pulse duration, since these two sets of experiments are performed with substantially different pulse durations, 100 ns and 190 fs, respectively. We show that inelastic higher-order effects play a role in the experiment with 100 ns laser pulses (the probed structure is that of the electrolyte solution that is modified by a laser pulse), while in the experiment with 190 fs laser pulses, only the elastic second-order response is measured (probing the unperturbed water structure).

Contributory factors in surgical incidents as delineated by a confidential reporting system.

Background Confidential reporting systems play a key role in capturing information about adverse surgical events. However, the value of these systems is limited if the reports that are generated are not subjected to systematic analysis. The aim of this study was to provide the first systematic analysis of data from a novel surgical confidential reporting system to delineate contributory factors in surgical incidents and document lessons that can be learned. Methods One-hundred and forty-five patient safety incidents submitted to the UK Confidential Reporting System for Surgery over a 10-year period were analysed using an adapted version of the empirically-grounded Yorkshire Contributory Factors Framework. Results The most common factors identified as contributing to reported surgical incidents were cognitive limitations (30.09%), communication failures (16.11%) and a lack of adherence to established policies and procedures (8.81%). The analysis also revealed that adverse events were only rarely related to an isolated, single factor (20.71%) - with the majority of cases involving multiple contributory factors (79.29% of all cases had more than one contributory factor). Examination of active failures - those closest in time and space to the adverse event - pointed to frequent coupling with latent, systems-related contributory factors. Conclusions Specific patterns of errors often underlie surgical adverse events and may therefore be amenable to targeted intervention, including particular forms of training. The findings in this paper confirm the view that surgical errors tend to be multi-factorial in nature, which also necessitates a multi-disciplinary and system-wide approach to bringing about improvements.

On site remediation of a fuel spill and soil reuse in Antarctica.

The first large-scale remediation of fuel contamination in Antarctica treated 10000L of diesel dispersed in 1700t of soil, and demonstrated the efficacy of on-site bioremediation. The project progressed through initial site assessment and natural attenuation, passive groundwater management, then active remediation and the managed reuse of soil. Monitoring natural attenuation for the first 12years showed contaminant levels in surface soil remained elevated, averaging 5000mg/kg. By contrast, in five years of active remediation (excavation and biopile treatment) contaminant levels decreased by a factor of four. Chemical indicators showed hydrocarbon loss was apportioned to both biodegradation and evaporative processes. Hydrocarbon degradation rates were assessed against biopile soil temperatures, showing a phase of rapid degradation (first 100days above soil temperature threshold of 0°C) followed by slower degradation (beyond 100days above threshold). The biopiles operated successfully within constraints typical of harsh climates and remote sites, including limitations on resources, no external energy inputs and short field seasons. Non-native microorganisms (e.g. inoculations) and other organic materials (e.g. bulking agents) are prohibited in Antarctica making this cold region more challenging for remediation than the Arctic. Biopile operations included an initial fertiliser application, biannual mechanical turning of the soil and minimal leachate recirculation. The biopiles are a practical approach to remediate large quantities of contaminated soil in the Antarctic and already 370t have been reused in a building foundation. The findings presented demonstrate that bioremediation is a viable strategy for Antarctica and other cold regions. Operators can potentially use the modelled relationship between days above 0°C (threshold temperature) and the change in degradation rates to estimate how long it would take to remediate other sites using the biopile technology with similar soil and contaminant types.

Protein-Derived Acetaminophen-Cysteine Can Be Detected After Repeated Supratherapeutic Ingestion of Acetaminophen in the Absence of Hepatotoxicity.

UNLABELLED: Generation of protein-derived acetaminophen-cysteine (APAP-CYS) is reported after ingestion of large and therapeutic dosages of acetaminophen in healthy and in liver-damaged patients. The incidence of protein-derived APAP-CYS adducts in repeated supratherapeutic dosages of APAP is not known. METHODS: for 12 months, a standardized and comprehensive questionnaire was used to interview every consecutive patient at a pain management clinic. Patients found to ingest more than 4 g of APAP per day for a minimum of 14 consecutive days at the time of the encounter were invited to have blood drawn for hepatic transaminases and APAP-CYS adduct levels. Twelve subjects out of 990 interviewees met inclusion criteria. Ten of the 12 had measurable protein-derived APAP-CYS, none had evidence of liver injury. Patients that ingest repeated supratherapeutic amounts of APAP over several weeks may generate APAP-CYS protein adducts in the absence of hepatic injury.

A practical guide to expedition medical planning.

Expedition medical planning is integral in ensuring participant safety and maximising the likelihood of achieving the expedition aims. The task of producing a medical plan will often fall to a medical officer of limited experience. The aim of this article is to provide a concise, practical guide to aid junior medical officers (MOs) in forming a robust and pragmatic medical plan.

Essential veterinary education in the welfare of food production animals.

The primary responsibility of veterinarians is to the animals in their care, so veterinary students need to be aware of important issues and factual information relevantto animal welfare. Veterinarians have tended to concentrate on physical aspects of welfare, but also need to take account of mental aspects (including pain) and naturalness. A crucial first step in animal welfare education is to encourage students to examine the interactions between welfare science, ethics and policy. Scientific measures of welfare include physiological, immunological, behavioural, disease and productivity. Welfare ethics includes consideration of different ethical theories and of professional ethics. Understanding of policy involves awareness of legislation, codes of practice and farm assurance programmes. As well as utilising their education in their clinical practice, veterinarians may expectto have an important role in influencing policy and standards in the wider world. It is recommended that animal welfare should be taught as a clearly defined academic subject within the curriculum.

Therapeutic opportunities in noncutaneous melanoma.

Recent evidence suggests that the biology of noncutaneous melanoma differs significantly from cutaneous melanoma and may provide therapeutic opportunity. The most frequent sites of origin of noncutaneous melanoma are the eye and mucosal surfaces. Although noncutaneous melanomas are an uncommon group of cancers (representing less than 10% of all melanomas) a greater understanding of their genetic and molecular abnormalites is being translated into novel treatment strategies. These developments are important because there is currently no effective systemic therapy for noncutaneous melanoma. Significant attention has been focused on the role of c-kit (KIT, CD117), a transmembrane receptor with tyrosine kinase activity. In vitro and ex vivo evidence suggests that c-kit is frequently expressed/over expressed/mutated in noncutaneous melanoma. Anti-tumour effects with c-kit inhibitors are seen in pre-clinical models. A variety of multitargeted kinase inhibitors which have activity against c-kit are currently in early phase clinical trials in metastatic ocular, mucosal and acral melanoma. The few case reports of significant clinical activity with targeted therapies provides hope that greater understanding of the biology of noncutaneous melanoma can be translated into effective treatment.

Sci-Thurs PM: Delivery-05: One year of learning from incidents.

The aim of this study is to quantify the effect of an incident learning system in radiation therapy. The system is designed to detect all occurrences of "an unwanted or unexpected change from a normal system behaviour that causes or has the potential to cause an adverse effect to persons or equipment". Our application to radiation therapy defines 5 incident types, four levels of severity and four work domains where errors discovered during routine quality assurance within each domain were not classified as incidents. During 2007, we recorded, corrected, investigated, determined root cause and learned from 657 incidents. The vast majority of these incidents were classified as potential minor clinical incidents having little or no impact on patient treatment. The value of the system lies in the application of the learning portion of the investigation. We demonstrated a dramatic reduction in the rate of more severe incidents by the implementation of several simple tools. Our results also show a reduction of incidents on accelerators treating essentially a single disease site. The only treatment unit treating with both image guidance and intensity modulation recorded the fewest incidents while the cobalt unit with the least technological assistance recorded three times the average treatment unit incidents with a higher severity. Additionally, although the rate of incidents at the point of treatment delivery was low, the impact of those incidents was substantially higher than that of incidents originating during treatment planning. This system has proven to be a powerful program management tool.

Development of antibodies for cancer therapy.

Antibody therapies have become an important component in the management of malignant disease. Recombinant technology offers enormous opportunities to tailor antibodies to meet clinical requirements. This includes the reduction of immunogenicity and the development of smaller antibody fragments that can be incorporated into fusion proteins. Antibodies can block tumour growth factors or their receptors, activate immunological attack on the tumour, or be used to deliver payloads such as radioisotopes, cytotoxic drugs or toxins. Pretargeting includes streptavidin/biotin systems and antibody-directed enzyme prodrug therapy (ADEPT). ADEPT uses an antibody-enzyme complex to deliver a prodrug-activating enzyme to tumours for selective prodrug conversion at the tumour site. New antibody targets, refined antibodies, antibody fusion proteins, combination therapies and the use of antibodies as adjuvant therapy are important topics in the development of antibody therapy against cancer.

Fitting the linear-quadratic model to detailed data sets for different dose ranges.

Survival curve behaviour and degree of correspondence between the linear-quadratic (LQ) model and experimental data in an extensive dose range for high dose rates were analysed. Detailed clonogenic assays with irradiation given in 0.5 Gy increments and a total dose range varying from 10.5 to 16 Gy were performed. The cell lines investigated were: CHOAA8 (Chinese hamster fibroblast cells), U373MG (human glioblastoma cells), CP3 and DU145 (human prostate carcinoma cell lines). The analyses were based on chi2-statistics and Monte Carlo simulation of the experiments. A decline of LQ fit quality at very low doses (<2 Gy) is observed. This result can be explained by the hypersensitive effect observed in CHOAA8, U373MG and DU145 data and an adaptive-type response in the CP3 cell line. A clear improvement of the fit is discerned by removing the low dose data points. The fit worsening at high doses also shows that LQ cannot explain this region. This shows that the LQ model fits better the middle dose region of the survival curve. The analysis conducted in our study reveals a dose dependency of the LQ fit in different cell lines.

Animal welfare: the role of non-governmental organisations.

The welfare of animals is of interest to many people in most parts of the world. Concern about the way that animals are treated will depend on many factors, including socio-economic conditions, culture, religion and tradition. The World Organisation for Animal Health (OIE) is committed to ensuring that all animal welfare standards are science-based, but recognises that these other factors must also be taken into account. The International Coalition for Farm Animal Welfare (ICFAW) was formed to represent the interests of non-governmental animal welfare organisations from most corners of the globe and opinions, comment and information from these animal welfare organisations will play a part in the OIE decision-making process. In coming together for this purpose it was recognised that the views of the various member organisations of ICFAW vary depending on which part of the world they come from. The authors provide information about the situation in three continents: Africa, North America and Europe. This information includes details of relevant legislation, farming practices, and educational and campaign programmes developed by both animal welfare non-governmental organisations and governments. The authors also look to the future to see what issues may influence the way that farm animals are reared, transported and slaughtered.

Improving risk disclosure during the consent process.

OBJECTIVES: To provide guidance about the risks which should be disclosed to patients and documented during the consent process. METHODS: The Delphi Consensus Technique was used to decide what constitutes mandatory risk disclosure for three index procedures. Documentation of risk on consent forms was audited and compared to these locally agreed standards. A four stage strategy for change was undertaken following which practice was reviewed. RESULTS: Mean mandatory risk documentation rose from 61.2% (95% CI: 58.1-64.4) pre-intervention, to 78.1% (95% CI: 72.6-83.6) post-intervention (ccc2; P < 0.001). CONCLUSIONS: Although we demonstrated some benefit from this simple approach, the need for pragmatic means of achieving and sustaining complete discussion and documentation of risks across all surgical interventions based on universally accepted standards remains.

Left atrial phaeochromocytoma.

Phaeochromocytomas of the heart are very rare. This report describes the case of a 69 year old woman presenting with persistent hypertension and a left atrial phaeochromocytoma diagnosed by 131I-metaiodobenzylguanidine scintigraphy scanning. She was successfully treated by surgical excision with the aid of cardiopulmonary bypass and perioperative alpha and beta adrenergic blockade.

Analysis of fentanyl and norfentanyl in human plasma by liquid chromatography-tandem mass spectrometry using electrospray ionization.

This report describes a sensitive and specific high-performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry (MS-MS) method for the detection of subnanogram concentrations of fentanyl and its metabolite norfentanyl in human plasma. The assay was based on a liquid-liquid extraction of 0.5 mL of human plasma, with a lower limit of quantitation (LLOQ) of 0.05 ng/mL. Sample extracts were analyzed using a ThermoQuest TSQ MS-MS interfaced with a Hewlett-Packard series 1100 HPLC and a Phenomenex (30 x 2.00-mm, 5 microLuna C18(2)) column. The intra-assay precision and accuracy ranged from 2.1 to 12.5% for both analytes at concentrations of 0.1, 0.5, 1.0, and 10 ng/mL. The interassay accuracy and precision ranged from 7.34 to 10.95%.

Surgical experience and supervision may influence the quality of lower limb amputation.

AIM: Only half of those patients undergoing major lower limb amputations for peripheral vascular disease (PVD) are likely to mobilise on a prosthesis. This study aimed to determine whether a surgeon's experience influenced the quality of the residual limb and thus the likelihood of the stump being suitable for a prosthesis. METHODS: All patients undergoing major lower limb amputations for PVD were recruited prospectively, between August 1992 and July 1996. Following surgery, patients were categorised, by a consultant in rehabilitation medicine, as potentially suitable (group 1) or unsuitable (group II) for rehabilitation. Patients in group I were further assessed by prosthetists for limb fitting. RESULTS: A total of 217 patients underwent 260 amputations for PVD between 1992 and 1996: transfemoral (TFA) 131, trans-tibial (TTA) 127, and through-knee (TKA) in 2. The 30-day mortality was 12% (n = 27). Following surgery, 109 patients were assigned to group I (51%), and 81 patients to group II (37%). The proportion of junior surgeons performing surgery was similar for patients in both groups. Twenty-three amputation stumps (9%) required revision or conversion to a higher level within 30 days. Revisions or conversions were significantly more frequent where the original operation had been performed by an unsupervised junior surgeon rather than a senior surgeon (P = 0.009). The rate of defective amputations compromising limb fitting also reached significance when unsupervised junior and senior surgeons were compared (P = 0.04). CONCLUSIONS: Rehabilitation of the relatively few amputees who reach the stage of limb fitting is hindered by poor surgical technique in a large proportion of cases. Patients operated on by a more experienced surgeon had a better chance of mobilising without revision or conversion surgery.