Observation of asphalt binder microstructure with ESEM.

The observation of asphalt binder with the environmental scanning electron microscope (ESEM) has shown the potential to observe asphalt binder microstructure and its evolution with binder aging. A procedure for the induction and identification of the microstructure in asphalt binder was established in this study and included sample preparation and observation parameters. A suitable heat-sampling asphalt binder sample preparation method was determined for the test and several stainless steel and Teflon sample moulds developed, finding that stainless steel was the preferable material. The magnification and ESEM settings conducive to observing the 3D microstructure were determined through a number of observations to be 1000×, although other magnifications could be considered. Both straight run binder (PG 58-28) and an air blown oxidised binder were analysed; their structures being compared for their relative size, abundance and other characteristics, showing a clear evolution in the fibril microstructure. The microstructure took longer to appear for the oxidised binder. It was confirmed that the fibril microstructure corresponded to actual characteristics in the asphalt binder. Additionally, a 'bee' micelle structure was found as a transitional structure in ESEM observation. The test methods in this study will be used for more comprehensive analysis of asphalt binder microstructure.

AAGBI: Safer pre-hospital anaesthesia 2017: Association of Anaesthetists of Great Britain and Ireland.

Pre-hospital emergency anaesthesia with oral tracheal intubation is the technique of choice for trauma patients who cannot maintain their airway or achieve adequate ventilation. It should be carried out as soon as safely possible, and performed to the same standards as in-hospital emergency anaesthesia. It should only be conducted within organisations with comprehensive clinical governance arrangements. Techniques should be straightforward, reproducible, as simple as possible and supported by the use of checklists. Monitoring and equipment should meet in-hospital anaesthesia standards. Practitioners need to be competent in the provision of in-hospital emergency anaesthesia and have supervised pre-hospital experience before carrying out pre-hospital emergency anaesthesia. Training programmes allowing the safe delivery of pre-hospital emergency anaesthesia by non-physicians do not currently exist in the UK. Where pre-hospital emergency anaesthesia skills are not available, oxygenation and ventilation should be maintained with the use of second-generation supraglottic airways in patients without airway reflexes, or basic airway manoeuvres and basic airway adjuncts in patients with intact airway reflexes.

Association of Anaesthetists of Great Britain and Ireland: Safe vascular access 2016.

Safe vascular access is integral to anaesthetic and critical care practice, but procedures are a frequent source of patient adverse events. Ensuring safe and effective approaches to vascular catheter insertion should be a priority for all practitioners. New technology such as ultrasound and other imaging has increased the number of tools available. This guidance was created using review of current practice and literature, as well as expert opinion. The result is a consensus document which provides practical advice on the safe insertion and removal of vascular access devices.

Frequency of delirium and subsyndromal delirium in an adult acute hospital population.

Background The frequency of full syndromal and subsyndromal delirium is understudied. Aims We conducted a point prevalence study in a general hospital. Method Possible delirium identified by testing for inattention was evaluated regarding delirium status (full/subsyndromal delirium) using categorical (Confusion Assessment Method (CAM), DSM-IV) and dimensional (Delirium Rating Scale-Revised-98 (DRS-R98) scores) methods. Results In total 162 of 311 patients (52%) screened positive for inattention. Delirium was diagnosed in 55 patients (17.7%) using DSM-IV, 52 (16.7%) using CAM and 58 (18.6%) using DRS-R98⩾12 with concordance for 38 (12.2%) individuals. Subsyndromal delirium was identified in 24 patients (7.7%) using a DRS-R98 score of 7-11 and 41 (13.2%) using 2/4 CAM criteria. Subsyndromal delirium with inattention (v. without) had greater disturbance of multiple delirium symptoms. Conclusions The point prevalence of delirium and subsyndromal delirium was 25%. There was modest concordance between DRS-R98, DSM-IV and CAM delirium diagnoses. Inattention should be central to subsyndromal delirium definitions.

Safety guideline: skin antisepsis for central neuraxial blockade.

Concise guidelines are presented that recommend the method of choice for skin antisepsis before central neuraxial blockade. The Working Party specifically considered the concentration of antiseptic agent to use and its method of application. The advice presented is based on previously published guidelines, laboratory and clinical studies, case reports, and on the known properties of antiseptic agents.

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells.

BACKGROUND: Effective treatment of prostate cancer (PCa) remains a major challenge due to chemoresistance to drugs including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Ethanol and ethanol extracts are known apoptosis inducers. However, cytotoxic effects of ethanol on PCa cells are unclear. METHODS: In this study we utilized PC3 and LNCaP cell culture models. We used immunohistochemical analysis, western blot analysis, reactive oxygen species (ROS) measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Cell Proliferation Assay, Annexin-V staining and flow cytometry for quantification of apoptosis. In vitro soft agar colony formation and Boyden chamber invasion assays were used. Tumorigenicity was measured in a xenotransplantation mouse model. RESULTS: Here, we demonstrate that ethanol enhances the apoptosis-inducing potential of TRAIL in androgen-resistant PC3 cells and sensitizes TRAIL-resistant, androgen sensitive LNCaP cells to apoptosis through caspase activation, and a complete cleavage of poly (ADP)-ribose polymerase, which was in association with increased production of ROS. The cytotoxicity of ethanol was suppressed by an antioxidant N-acetyl cystein pretreatment. Furthermore, ethanol in combination with TRAIL increased the expression of cyclin-dependent kinase inhibitor p21 and decreased the levels of Bcl-2 and phosphorylated-AKT. These molecular changes were accompanied by decreased proliferation, anchorage-independent growth and invasive potential of PC3 and LNCaP cells. In vivo studies using a xenotransplantation mouse model with PC3 cells demonstrated significantly increased apoptosis in tumors treated with ethanol and TRAIL in combination. CONCLUSIONS: Taken together, use of ethanol in combination with TRAIL may be an effective strategy to augment sensitivity to TRAIL-induced apoptosis in PCa cells.

Changes in transcriptional output of human peripheral blood mononuclear cells following resistance exercise.

Various types of exercise alter the population of circulating peripheral blood mononuclear cells (PBMCs) and change their transcriptional output. This work examines changes in PBMC populations and transcription in response to resistance exercise training (RET), and identify key transcriptional changes in PBMCs that may play a role in altering peripheral tissues in response to RET. Ten resistance-trained men (20-24 years), performed an acute bout of RET for ~30 min following a 12 h fast. Venous blood was sampled at rest, immediately following exercise, and at 2 h post-exercise and analyzed for total and differential leukocytes and global gene expression using Affymetrix Genechips. Results showed elevated leukocytes, monocytes, lymphocytes, and lactate values immediately post-exercise (P < 0.05) over baseline. At 2 h post-exercise, leukocytes, and granulocytes remained elevated (P < 0.05), whereas lymphocytes were lower than (P < 0.05) baseline values. Initial microarray results showed the greatest transcriptional changes in pathways related to immune response, inflammation, and cellular communication. The change in PBMC population (2 h time point) correlated with a dramatic decrease in the expression of CD160, and XCL1, markers of lymphocyte populations. At the 2 h recovery time point upregulation of matrix metalloproteinase 9, orosomucoid 1, dishevelled-associated activator of morphogenesis 2, and arginase 1 suggest an induction in muscle damage and repair during this time frame. These results demonstrate that an acute bout of RET disrupts cellular homeostasis, induces a transient redistribution of certain leukocytes, and results in transcriptional changes in PBMCs translating into systemic changes in response to RET.

Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia.

Heat shock protein 90 (Hsp90) is a molecular chaperone with many oncogenic client proteins. The small-molecule Hsp90 inhibitor alvespimycin, a geldanamycin derivative, is being developed for various malignancies. This phase 1 study examined the maximum-tolerated dose (MTD), safety and pharmacokinetic/pharmacodynamic profiles of alvespimycin in patients with advanced acute myeloid leukemia (AML). Patients with advanced AML received escalating doses of intravenous alvespimycin (8-32 mg/m(2)), twice weekly, for 2 of 3 weeks. Dose-limiting toxicities (DLTs) were assessed during cycle 1. A total of 24 enrolled patients were evaluable for toxicity. Alvespimycin was well tolerated; the MTD was 24 mg/m(2) twice weekly. Common toxicities included neutropenic fever, fatigue, nausea and diarrhea. Cardiac DLTs occurred at 32 mg/m(2) (elevated troponin and myocardial infarction). Pharmacokinetics revealed linear increases in C(max) and area under the curve (AUC) from 8 to 32 mg/m(2) and minor accumulation upon repeated doses. Pharmacodynamic analyses on day 15 revealed increased apoptosis and Hsp70 levels when compared with baseline within marrow blasts. Antileukemia activity occurred in 3 of 17 evaluable patients (complete remission with incomplete blood count recovery). The twice-weekly administered alvespimycin was well tolerated in patients with advanced AML, showing linear pharmacokinetics, target inhibition and signs of clinical activity. We determined a recommended phase 2 dose of 24 mg/m(2).

Unanticipated difficult airway management in anaesthetised patients: a prospective study of the effect of mannequin training on management strategies and skill retention.

This prospective study on a medium-fidelity simulator (SimMan, Laerdal Medical Corporation, Wappingers Falls, NY, USA) examined the management of unanticipated difficult airway by 21 anaesthetists and the effect of training in this context. There were two scenarios investigated: 'cannot intubate, can ventilate' (CI) and 'cannot intubate, cannot ventilate' (CICV). Following initial evaluation, volunteers underwent training in the 'Difficult Airway Society' (DAS) algorithms and associated technical skills. At 6-8 weeks and 6-8 months, performance was compared with the initial evaluation. There was a more structured approach following training (p < 0.05), which was sustained at 6-8 months, but only for the CICV scenario (p < 0.01). In CI, use of standard and intubating laryngeal mask airway increased following training (p = 0.021). This was sustained over time (p = 0.01). In both scenarios there was a reduced incidence of equipment misuse (p < 0.0005), which was sustained over time (p < 0.0001). We conclude that simulation-based training significantly improves performance for at least 6-8 weeks. Training should be repeated at intervals of 6 months or less.

Surgical vs wire-guided cricothyroidotomy: a randomised crossover study of cuffed and uncuffed tracheal tube insertion.

Using an airway mannequin and artificial lung model, we compared surgical cricothyroidotomy with a 6.0-mm cuffed Portex tracheostomy tube with wire-guided cricothyroidotomy using a 5.0-mm cuffed Melker or 6.0-mm uncuffed Melker tube. The trial was carried out by 27 anaesthetists using a randomised, crossover design. Surgical cricothyroidotomy proved significantly faster (mean (SD) time to first breath 44.3 (12.5) s for Portex surgical, 87.2 (21.6) s for cuffed Melker, 87.8 (19.2) s for uncuffed Melker, p < 0.001). With a standardised ventilator model, the cuffed tubes provided more effective ventilation (mean (SD) tidal volume 446 (41) ml Portex, 436 (52) ml cuffed Melker, 19 (5) ml uncuffed Melker, p < 0.001). Fourteen of the participants preferred the wire-guided system. We conclude that, in this model, a cuffed device is preferable when cricothyroidotomy is needed. In addition, the surgical method is quicker than a wire-guided approach.