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The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation^{1,2}. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole^3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of 8.4_{-1.1}^{+0.5} Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow., 50 pages, 18 figures, 3 tables, author's version of the paper published in Nature

Purpose: To report the 12-month safety and efficacy outcomes of the investigational device exemption trial evaluating an implantable below-the-knee (BTK) dissection repair device. Materials and Methods: The prospective, multicenter, single-arm Tack-Optimized Balloon Angioplasty (TOBA) II BTK study ( ClinicalTrials.gov identifier NCT02942966) evaluated the Tack Endovascular System in the BTK arteries vs objective performance goals derived from a systematic review of BTK angioplasty literature. Patients presenting with Rutherford category 3–5 ischemia were eligible and were enrolled during the procedure if angioplasty resulted in dissection(s) of the BTK arteries. Between February 2017 and December 2018, the study enrolled 233 patients (mean age 74.4±10.0 years; 157 men). Most lesions (93.8%) were de novo; almost half (118/248, 47.6%) were total occlusions. Mean target lesion length was 80±49 mm. Moderate to severe calcium was present in 89 (35.8%) lesions. The 30-day primary safety endpoint was a composite of major adverse limb events (MALE) and all-cause perioperative death (POD). The primary efficacy endpoint was a composite of MALE at 6 months and 30-day POD. These safety and efficacy endpoints were assessed at 12 months as observational endpoints along with amputation-free survival (AFS), freedom from clinically-driven target lesion revascularization (CD-TLR), vessel patency, and changes from baseline in clinical and quality of life measures. Results: All patients had post-PTA dissection and received at least 1 Tack implant (range 1 to 16). The angiographic core laboratory noted successful resolution of 100% of the 341 treated dissections. At 12 months, 93.4% (170/182) of patients remained free of the composite endpoint of MALE + POD. Tacked segment patency was 81.3% and limb salvage was 96.8% at 12 months; freedom from CD-TLR and AFS were 83.1% and 89.3%, respectively. Sustained Rutherford category improvement was reported in 82.4% of evaluated patients, with 62.4% improving ≥3 categories (p

Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU:50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.

Algae-based products have applications in the food and pharmaceutical industries, bioremediation of waste streams and biofuel production. Drying has been recognised to constitute the largest energy cost in algae processing, yet there is limited data or modelling characterising the drying kinetics of macroalgae. This research modelled the equilibrium moisture content of two macroalgae species, Ulva ohnoi, a saltwater alga and Oedogonium intermedium, a freshwater alga. The Guggenheim&ndash, Anderson&ndash, de Boer model was found to best represent experimental equilibrium moisture contents. Drying rate curves obtained under both convective and radiative conditions were fitted to an analytical solution of Fick&rsquo, s second law, including the modelled equilibrium moisture values. Effective diffusivity values for the two species are presented.

With recent downsizing of talented professionals and the power of globalization to provide opportunities for more underdeveloped countries, the gig economy is a source of influence in today�s generation of professionals. Online outsourcing media have shown to be valuable resources for companies who need a specific set of skills for a limited period. This case study evaluates Upwork.com, one of the leading freelance websites in the gig economy; this article provides insights on how others should evaluate the power of this new economy in terms of opportunities for small businesses, entrepreneurs, and freelancers. Upwork has led the pack by providing a flexible platform for freelancers worldwide, including coders, writers, and web developers, putting businesses in touch with reasonably priced workers. The study begins by exploring the attributes of the gig economy. Data collection is achieved through qualitative analysis. The application of these conclusions could increase the survival rate of new freelancers on Upwork.com and in the gig economy. The study is significant because this research widens contemporary assumptions about strategic thinking for individuals engaged in e-commerce.

To determine predictors of inability to return to work due to health six-months after intensive care admission; and compare functional recovery between patients who had not returned to work and employed patients.Participants were working adults admitted to ICU who received24 h of mechanical ventilation. Outcomes included inability to return to work due to health at six-months post-ICU admission, disability, health status, anxiety, depression and post-traumatic stress.Of 107 patients, 31 (29%) were unable to return to work due to health at six-months after ICU admission. Predictors of inability to return to work included longer hospital stay (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.08; P = .004); lower Glasgow Coma Scale (GCS) at admission (OR, 0.86; CI, 0.75-0.99; P = .03); and admission due to major trauma (OR, 8.83; CI, 2.57-30.38; P .001). Compared to employed patients, those who had not returned to work reported higher levels of disability and psychological distress, and poorer health-related quality of life.Major trauma, lower GCS and increased hospital length of stay predicted inability to return to work due to health at six-months post-ICU admission. Compared to employed patients, those who had not returned to work reported poorer functional recovery.

M87 is the best source in which to study a jet at high resolution in gravitational units because it has a very high mass black hole and is nearby. The angular size of the black hole is second only to Sgr A*, which does not have a strong jet. The jet structure is edge brightened with a wide opening angle base and a weak counterjet. We have roughly annual observations for 17 years plus intensive monitoring at three week intervals for a year and five day intervals for 2.5 months made with the Very Long Baseline Array (VLBA) at 43 GHz. The inner jet shows very complex dynamics, with apparent motions both along and across the jet. Speeds from zero to over 2c are seen, with acceleration observed over the first 3 milli-arcseconds. The counterjet decreases in brightness much more rapidly than the main jet, as is expected from relativistic beaming in an accelerating jet oriented near the line-of-sight. Details of the structure and dynamics are discussed. The roughly annual observations show side-to-side motion of the whole jet with a characteristic time scale of about 9 years., 11 pages, 7 figures. Published in a special issue of Galaxies which is the proceedings of "Blazars through Sharp Multi-Wavelength Eyes" edited by J. L. Gomez, A. P. Marscher, and S. G. Jorstad

In the Results section, under the subheading “Return to work or usual activities”, the second sentence should read.

With an emphasis on reducing fossil fuel consumption and emissions, major delivery service corporations have begun deploying and operating Class 6 zero emissions delivery vans. Battery electric delivery vans are currently available, but their range is a limitation and doesn't offer flexibility in assigning vehicles to delivery routes. Fuel cell hybrid delivery vans offer a zero emissions solution with extended range and route planning flexibility. In a competitive market, a delivery van design that trades the fuel cell and battery size, performance, and cost is critical to the success and adoption of these zero emissions trucks. This paper outlines a systematic approach using real world operational data and duty cycles to properly size the fuel cell and battery for a zero emissions hybrid delivery van. The approach uses real world GPS data to define routes and duty cycles, along with vehicle powertrain models to assess performance capabilities. The study suggests that a 32 kW fuel cell power system paired with a 49 kWh battery energy storage system and 15 kg of hydrogen storage is a desired option to complete the most demanding parcel and delivery duty cycles.

To use the World Health Organisation’s International Classification of Functioning to measure disability following critical illness using patient-reported outcomes. A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation’s Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU. We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P

The Clinch River is located in northeastern Tennessee (TN) and southwestern Virginia (VA) of the United States, and contains a diverse mussel assemblage of 46 extant species, including 20 species listed as federally endangered. To facilitate quantitative monitoring of the fauna, quadrat data were collected from 2004 to 2009 at 18 sites in the river, including 12 sites in TN and 6 sites in VA. Thirty-eight mussel species were collected alive in total from quadrat samples taken annually at sites in the TN section of the river. Over the five-year study period, mussel density averaged 25.5 m−2 at all sites sampled in TN. In contrast, mussel density averaged only 3.1 m−2 at sites sampled in VA. The best historical site in VA was Pendleton Island in Scott County, where mussel density was estimated as high as 25 m−2 in 1979, comparable to current densities recorded in TN. Mussel densities are now

This study investigated the relative efficacy of postgame recovery modalities on jump height performance and subjective ratings of muscle soreness and muscle damage at 1, 18, and 42 hours after professional rugby league competition games. Twenty-one professional rugby league players performed 3 different postmatch recovery modalities: cold water immersion (CWI), contrast water therapy (CWT), and active recovery (ACT). The effects of the recovery treatments were analyzed with mixed modeling including a covariate (fatigue score) to adjust for changes in the intensity of each match on the postmatch values of the dependent variables of interest. Standardization of effects was used to make magnitude-based inferences, presented as mean with ±90% confidence limits. Cold water immersion and CWT clearly recovered jump height performance (CWI 2.3 ± 3.7%; CWT 3.5 ± 4.1%), reduced muscle soreness (CWI -0.95 ± 0.37; CWT -0.55 ± 0.37), and decreased creatine kinase (CWI -11.0 ± 15.1%; CWT 18.2 ± 20.1%) by 42 hours postgame compared with ACT. Contrast water therapy was however clearly more effective compared with CWI on the recovery of muscle soreness and creatine kinase by 42 hours postgame. Based on these findings, CWT recovery is recommended postmatch for team rugby sports.

V. Pettilä on työryhmän ARISE Investigators jäsen. Study objective: The influence of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) on the conduct of future sepsis research is unknown. We seek to examine the potential effect of the new definitions on the identification and outcomes of patients enrolled in a sepsis trial. Methods: This was a post hoc analysis of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial of early goal-directed therapy that recruited 1,591 adult patients presenting to the emergency department (ED) with early septic shock diagnosed by greater than or equal to 2 systemic inflammatory response syndrome criteria and either refractory hypotension or hyperlactatemia. The proportion of participants who would have met the Sepsis-3 criteria for quick Sequential Organ Failure Assessment (qS0FA) score, sepsis (an increased Sequential Organ Failure Assessment score >= 2 because of infection) and septic shock before randomization, their baseline characteristics, interventions delivered, and mortality were determined. Results: There were 1,139 participants who had a qSOFA score of greater than or equal to 2 at baseline (71.6% [95% confidence interval [Cl) 69.4% to 73.8%]). In contrast, 1,347 participants (84.7% [95% CI 82.9% to 86.4%]) met the Sepsis-3 criteria for sepsis. Only 1,010 participants were both qSOFA positive and met the Sepsis-3 criteria for sepsis (63.5% [95% CI 61.1% to 65.8%]). The Sepsis-3 definition for septic shock was met at baseline by 203 participants (12.8% [95% CI 11.2% to 14.5%]), of whom 175 (86.2% [95% CI 81.5% to 91.0%]) were also qSOFA positive. Ninety-day mortality for participants fulfilling the Sepsis-3 criteria for sepsis and septic shock was 20.4% (95% CI 18.2% to 22.5%) (274/1,344) and 29.6% (95% CI 23.3% to 35.8% [60/203]) versus 9.4% (95% CI 5.8% to 13.1%) (23/244) and 17.1% (95% CI 15.1% to 19.1% [237/1,388]), respectively, for participants not meeting the criteria (risk differences 11.0% [95% CI 6.2% to 14.8%] and 12.5% [95% CI 6.3% to 19.4%], respectively). Conclusion: Most ARISE participants did not meet the Sepsis-3 definition for septic shock at baseline. However, the majority fulfilled the new sepsis definition and mortality was higher than for participants not fulfilling the criteria. A quarter of participants meeting the new sepsis definition did not fulfill the qSOFA screening criteria, potentially limiting its utility as a screening tool for sepsis trials with patients with suspected infection in the ED. The implications of the new definitions for patients not eligible for recruitment into the ARISE trial are unknown.

Sediment toxicity tests were conducted to assess potential effects of contaminants associated with coal mining or natural gas extraction activities in the upper Tennessee River basin and eastern Cumberland River basin in the United States. Test species included two unionid mussels (rainbow mussel, Villosa iris, and wavy-rayed lampmussel, Lampsilis fasciola, 28-d exposures), and the commonly tested amphipod, Hyalella azteca (28-d exposure) and midge, Chironomus dilutus (10-d exposure). Sediments were collected from seven test sites with mussel communities classified as impacted and in proximity to coal mining or gas extraction activities, and from five reference sites with mussel communities classified as not impacted and no or limited coal mining or gas extraction activities. Additional samples were collected from six test sites potentially with high concentrations of polycyclic aromatic hydrocarbons (PAHs) and from a test site contaminated by a coal ash spill. Mean survival, length, or biomass of one or more test species was reduced in 10 of 14 test samples (71%) from impacted areas relative to the response of organisms in the five reference samples. A higher proportion of samples was classified as toxic to mussels (63% for rainbow mussels, 50% for wavy-rayed lampmussels) compared with amphipods (38%) or midge (38%). Concentrations of total recoverable metals and total PAHs in sediments did not exceed effects-based probable effect concentrations (PECs). However, the survival, length, or biomasses of the mussels were reduced significantly with increasing PEC quotients for metals and for total PAHs, or with increasing sum equilibrium-partitioning sediment benchmark toxic units for PAHs. The growth of the rainbow mussel also significantly decreased with increasing concentrations of a major anion (chloride) and major cations (calcium and magnesium) in sediment pore water. Results of the present study indicated that (1) the findings from laboratory tests were generally consistent with the field observations of impacts on mussel populations; (2) total recoverable metals, PAHs, or major ions, or all three in sediments might have contributed to the sediment toxicity; (3) the mussels were more sensitive to the contaminants in sediments than the commonly tested amphipod and midge; and (4) a sediment toxicity benchmark of 1.0 based on PECs may not be protective of mussels.

We explore whether Machiavellianism—a personality trait which describes the extent to which individuals ignore values and ethical considerations when the ends justify the means—will influence their responses to their employing organizations’ failure to fulfil promised obligations (psychological contracts). Specifically, we draw on psychological contracts theory and the group value model to argue that Machiavellianism will moderate the relationships between psychological contract breach and (1) organizational identification; and (2) organizational disidentification. We tested our hypotheses in a study of 262 employees from various organizations at two points in time. We found that psychological contract breach was negatively related to organizational identification and positively related to organizational disidentification. Furthermore, employees with higher levels of Machiavellianism tended to disidentify with their organizations to a greater extent (at Time 2) in response to psychological contract breach (at Time 1) than did employees with low levels of Machiavellianism. Machiavellianism did not moderate the relationship between psychological contract breach and organizational identification. Our study contributes to extant research exploring the importance of Machiavellianism in the workplace. Specifically, we show that employees with high levels of Machiavellianism are more likely to disidentify in response to psychological contract breach but do not tend to identify to a lesser degree. This study builds on the extant research exploring individual differences in the psychological contract dynamics by considering Machiavellianism as a moderator of the breach–outcome relationship.

The differentiation of therapeutic monoclonal antibodies in an increasingly competitive landscape requires optimization of clinical efficacy combined with increased patient convenience. We describe here the generation of MEDI5117, a human anti-interleukin (IL)-6 antibody generated by variable domain engineering, to achieve subpicomolar affinity for IL-6, combined with Fc (fragment crystallizable) engineering to enhance pharmacokinetic half-life. MEDI5117 was shown to be highly potent in disease-relevant cellular assays. The pharmacokinetics of MEDI5117 were evaluated and compared to those of its progenitor, CAT6001, in a single-dose study in cynomolgus monkeys. The antibodies were administered, either subcutaneously or intravenously, as a single dose of 5 mg/kg. The half-life of MEDI5117 was extended by approximately 3-fold, and clearance was reduced by approximately 4-fold when compared to CAT6001. MEDI5117 therefore represents a potential 'next-generation' antibody; future studies are planned to determine the potential for affinity-driven efficacy and/or less frequent administration.

Geodetic very long baseline interferometry (VLBI) delivers time series of station positions and Earth orientation parameters. These series offer a viable and precise way to study Earth crustal and core dynamics and to support space navigation. Their accuracy is degraded by instrumental errors, of which polarization leakage is considered to be one of the largest that is not yet being addressed. Its effect on the data can be corrected, provided one knows the leakage characteristics of the receivers. For this purpose, we designed a VLBI session to measure the polarization leakage at 15 geodetic and very long baseline array stations over the frequency range from 8,212.99 to 8,932.99 MHz. We describe the polarization leakage measurements and the algorithm that was implemented to correct for its effect on the geodetic delay observables. Subsequently, we applied the correction for polarization leakage to the same data that were used to determine the leakage and checked for the resulting improvement. From the measured leakage terms, one would expect polarization leakage to affect the group delay measurements in 90% of the cases by 1.6 ps or less. This proved to be below the statistical noise in our single VLBI session, and hence, an improvement from the correction could not be detected. Applying this analysis in the context of VLBI2010, we provide a specification for the allowable polarization leakage to achieve the target submillimetre accuracy.

The central radio source in M87 provides the best opportunity to study jet formation because it has a large angular size for the gravitational radius of the black hole and has a bright jet that is well resolved by VLBI observations. We present intensive monitoring observations from 2007 and 2008, plus roughly annual observations that span 17 years, all made with the the Very Long Baseline Array at 43 GHz with a resolution of about 30 by 60 Rs. Our high-dynamic-range images clearly show the wide-opening-angle structure and the counter-jet. The jet and counter-jet are nearly symmetric in the inner 1.5 milli-arcseconds (mas; 0.12 pc in projection) with both being edge brightened. Both show deviations from parabolic shape in the form of an initial rapid expansion and subsequent contraction followed by further rapid expansion and, beyond the visible counter-jet, subsequent collimation. Proper motions and counter-jet/jet intensity ratios both indicate acceleration from apparent speeds of $\lesssim 0.5c$ to $\gtrsim 2c$ in the inner about 2 mas and suggest a helical flow. The jet displays a sideways shift with an approximately 8 to 10 year quasi-periodicity. The shift propagates outwards non-ballistically and significantly more slowly than the flow speed revealed by the fastest moving components. Polarization data show a systematic structure with magnetic field vectors that suggest a toroidal field close to the core., 49 pages, 25 figures (one double). 4 tables, 3 animations. Accepted for publication in the Astrophysical Journal. The animations are provided in the ancillary files

trans-Urocanic acid (UCA) acts as a chromophore for UV radiation in the epidermis and isomerizes to cis-UCA which then initiates some of the changes leading to UV-induced immunosuppression. The mechanism of the immunomodulation by cis-UCA is unknown at present, but one possibility is that the interaction between cis-UCA and keratinocytes causes the release of immunosuppressive cytokines locally. To test this hypothesis, PAM-212 cells, a murine keratinocyte cell line, were incubated with 0.10–100 μg/mL trans- and cis-UCA for 6 or 24 h, respectively. The expression of interleukin (IL)-10, transforming growth factor (TGF)-β and tumor necrosis factor (TNF)-α messenger RNA (mRNA) was then measured by reverse transcription-polymerase chain reaction in comparison with the mRNA for the house-keeping gene, β-actin. No change or significant induction of any of the cytokine messages occurred. However, the expression of IL-10 messenger RNA (mRNA) was induced 24 h after UVB irradiation (300 J/m2) and that of TNF-α mRNA occurred 6 h after treatment with phorbol myristate acetate. The expression of IL-10 protein was also examined by immunostaining in both PAM-212 cells and B16-F10 murine melanoma cells between 3 and 48 h after incubation with 10 and 100 μg/mL cis- and trans-UCA. No alteration was seen with either isomer at either concentration. In contrast, UVB irradiation of both cell lines resulted in a marked increase in intracellular IL-10 protein at 24 and 48 h. Therefore the upregulation of the immunosuppressive cytokines, IL-10, TNF-α and TGF-β, in keratinocytes is unlikely to be the mechanism by which cis-UCA induces immunosuppression in mice.

Introduction Despite studies demonstrating benefit, patients with femoral vascular catheters placed for continuous renal replacement therapy are frequently restricted from mobilization. No researchers have reported filter pressures during mobilization, and it is unknown whether mobilization is safe or affects filter lifespan. Our objective in this study was to test the safety and feasibility of mobilization in this population. Methods A total of 33 patients undergoing continuous renal replacement therapy via femoral, subclavian or internal jugular vascular access catheters at two general medical-surgical intensive care units in Australia were enrolled. Patients underwent one of three levels of mobilization intervention as appropriate: (1) passive bed exercises, (2) sitting on the bed edge or (3) standing and/or marching. Catheter dislodgement, haematoma and bleeding during and following interventions were evaluated. Filter pressure parameters and lifespan (hours), nursing workload and concern were also measured. Results No episodes of filter occlusion or failure occurred during any of the interventions. No adverse events were detected. The intervention filters lasted longer than the nonintervention filters (regression coefficient = 13.8 (robust 95% confidence interval (CI) = 5.0 to 22.6), P = 0.003). In sensitivity analyses, we found that filter life was longer in patients who had more position changes (regression coefficient = 2.0 (robust 95% CI = 0.6 to 3.5), P = 0.007). The nursing workloads between the intervention shift and the following shift were similar. Conclusions Mobilization during renal replacement therapy via a vascular catheter in patients who are critically ill is safe and may increase filter life. These findings have significant implications for the current mobility restrictions imposed on patients with femoral vascular catheters for renal replacement therapy. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12611000733976 (registered 13 July 2011) Electronic supplementary material The online version of this article (doi:10.1186/cc14001) contains supplementary material, which is available to authorized users.

Objective/Scope In Q4 2012, the 8” Teal dynamic riser required replacement. A project team was assembled to remove the existing riser and install a replacement. The riser was originally installed in the 1990's by divers based on the Anasuria Floating Production Storage Offloading (FPSO). The FPSO facilities that were used to provide diver access into the chain table area to secure the bend restrictor were no longer operational. Previous diver intervention at the chain table had experienced high levels of non-productive time, so a remote removal method to cut and lower the riser and bend restrictor to the seabed was pursued. Methods, Procedures, Process The project team initiated a concept study to set the challenge to release the riser from the FPSO remotely to a) reduce HSE risk; b) de-risk project by separating release campaign from recovery campaign and c) perform the work offshore using a very small team (FPSO bedding constraints was one of the reasons the team didn't use an air dive team to do it from the FPSO). The concept selected was largely based on a method used for removal of other similar risers in 1999 albeit that all that remained from that campaign was a PowerPoint presentation. The majority of engineering calculations and drawings could not be located. Results, Observations, Conclusions The tooling was designed, fabricated and tested in less than 6 months from award of contract to offshore operations. During the offshore campaign, various issues were encountered (e.g. incorrect ‘as built‘ documentation) but the remote removal campaign was a success with both the riser and its bend restrictor being removed from the FPSO without requiring any diver intervention, thus reducing the project costs and HSE exposure. Novel/Additive Information Lessons learned from the offshore campaign are being captured with the concept being further refined to allow the removal of the riser and bend restrictor without first having to cut and remove the topside riser end fitting. This should reduce the offshore operational time for any future riser removals and remove the risks associated with unknown internal condition of the riser.

Current immunosuppressive therapies act on T lymphocytes by modulation of cytokine production, modulation of signaling pathways or by inhibition of the enzymes of nucleotide biosynthesis. We have identified a previously unknown series of immunomodulatory compounds that potently inhibit human and rat T lymphocyte proliferation in vitro and in vivo in immune-mediated animal models of disease, acting by a novel mechanism. Here we identify the target of these compounds, the monocarboxylate transporter MCT1 (SLC16A1), using a strategy of photoaffinity labeling and proteomic characterization. We show that inhibition of MCT1 during T lymphocyte activation results in selective and profound inhibition of the extremely rapid phase of T cell division essential for an effective immune response. MCT1 activity, however, is not required for many stages of lymphocyte activation, such as cytokine production, or for most normal physiological functions. By pursuing a chemistry-led target identification strategy, we have discovered that MCT1 is a previously unknown target for immunosuppressive therapy and have uncovered an unsuspected role for MCT1 in immune biology.

The generation of reactive oxygen species has been implicated in ultraviolet radiation (UVR)-induced skin damage. In mice, increasing dietary selenium intake protects skin from UVR-induced DNA damage and photocarcinogenesis. We sought to determine whether selenium supplementation could protect keratinocytes from apoptosis resulting from exposure to broadband (TL20W/12) UVR. Unirradiated cultures contained 6.5 +/- 1% apoptotic cells; the maximum percentage of apoptotic cells (34 +/- 5%) was seen 16 h after UVR of 600 J/m(2). Under these conditions cell death from necrosis was 15 +/- 2.5% of the total cells. A 24-h preincubation with sodium selenite (10 nm(-1) microm) or selenomethionine (50 nm(-1) microm) protected cultured human keratinocytes from UVR-induced apoptosis. In primary keratinocytes the greatest reduction in apoptosis was found with 100 nm of either selenium compound (71% reduction in the numbers of total apoptotic cells; P < 0.01). Supplementation with 100-200 nm selenite or selenomethionine prevented UVR-induced apoptosis, but did not decrease the levels of UVR-induced p53, as measured by Western blotting. Collectively, this data suggests that selenium prevents UVR-induced cell death by inhibiting p53-independent cell death pathways.

The purpose of this study was to evaluate the safety and efficacy of excimer laser atherectomy (ELA) with adjunctive percutaneous transluminal angioplasty (PTA) versus PTA alone for treating patients with chronic peripheral artery disease with femoropopliteal bare nitinol in-stent restenosis (ISR).Femoropopliteal stenting has shown superiority to PTA for lifestyle-limiting claudication and critical limb ischemia, although treating post-stenting artery reobstruction, or ISR, remains challenging.The multicenter, prospective, randomized, controlled EXCITE ISR (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis) trial was conducted across 40 U.S. centers. Patients with Rutherford Class 1 to 4 and lesions of target lesion length ≥4 cm, vessel diameter 5 to 7 mm were enrolled and randomly divided into ELA + PTA and PTA groups by a 2:1 ratio. The primary efficacy endpoint was target lesion revascularization (TLR) at 6-month follow up. The primary safety endpoint was major adverse event (death, amputation, or TLR) at 30 days post-procedure.Study enrollment was stopped at 250 patients due to early efficacy demonstrated at a prospectively-specified interim analysis. A total of 169 ELA + PTA subjects (62.7% male; mean age 68.5 ± 9.8 years) and 81 PTA patients (61.7% male; mean age 67.8 ± 10.3 years) were enrolled. Mean lesion length was 19.6 ± 12.0 cm versus 19.3 ± 11.9 cm, and 30.5% versus 36.8% of patients exhibited total occlusion. ELA + PTA subjects demonstrated superior procedural success (93.5% vs. 82.7%; p = 0.01) with significantly fewer procedural complications. ELA + PTA and PTA subject 6-month freedom from TLR was 73.5% versus 51.8% (p0.005), and 30-day major adverse event rates were 5.8% versus 20.5% (p0.001), respectively. ELA + PTA was associated with a 52% reduction in TLR (hazard ratio: 0.48; 95% confidence interval: 0.31 to 0.74).The EXCITE ISR trial is the first large, prospective, randomized study to demonstrate superiority of ELA + PTA versus PTA alone for treating femoropopliteal ISR. (Randomized Study of Laser and Balloon Angioplasty Versus Balloon Angioplasty to Treat Peripheral In-stent Restenosis [EXCITE ISR]; NCT01330628).

Psoriasis is a disease marked by keratinocyte hyperproliferation, neutrophil and lymphocyte infiltration, and aberrant epidermal and dermal expression of cytokines. Previously, it has been shown that LIF appears to be involved in skin inflammation and can induce the expression of IL-8. We sought to determine whether expression of LIF is abnormal in lesional psoriatic skin and whether this correlates with the expression of IL-8. Using reverse transcription polymerase chain reaction, we measured the expression of LIF and IL-8 mRNA in biopsies from normal individuals, non-lesional psoriatic skin, and lesional psoriatic skin. No difference was seen between the expression of IL-8 and LIF in normal and in non-lesional psoriatic skin. However, LIF expression in lesional skin was increased 160% compared with normal biopsies or non-lesional skin (p < 0.001). Immunostaining of frozen sections showed that the expression of LIF protein was principally suprabasal and, in the majority of sections, concentrated mainly in the stratum corneum of the lesional skin, whereas it was mainly in the stratum spinosum of the normal/non-lesional skin. IL-8 mRNA expression did not differ between the non-lesional and normal skin, but expression in the lesional skin was 17.6-fold greater than in normal skin (p < 0.001), and this expression was correlated with the increased LIF expression (r = 0.67, p < 0.001). Although a significant negative correlation was demonstrated between LIF mRNA expression and the duration of the last outbreak of the disease, no other correlations were found between levels of cytokine expression and a variety of parameters including PASI score. These data suggest a role for keratinocyte LIF in the psoriatic lesion and a link between LIF and IL-8 expression.

Leukaemia inhibitory factor (LIF) and interleukin (IL)-8 possess activities which may contribute to the development of carcinomas. LIF can stimulate proliferation of some tumour cell lines and IL-8 is angiogenic. Using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we measured the expression of LIF and IL-8 mRNA in cultured normal keratinocytes (NKC) and the malignant carcinoma cells lines A431, SiHa, HeLa, and in biopsies of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin. Protein expression for LIF was assessed by immunohistochemistry in the biopsies. LIF mRNA expression was increased significantly (P < 0.01) in all carcinoma lines, except SiHa, compared with NKC but the IL-8 mRNA expression in carcinoma cell lines was similar to that in NKC. Expression of LIF mRNA was elevated in BCC and SCC compared with normal skin, but a significant difference was observed only between SCC and normal skin (P < 0.01). Both BCC and SCC showed significantly greater expression of IL-8 compared with normal skin (P < 0.01). There was no correlation between LIF and IL-8 mRNA expression either in BCCs or in SCCs. Immunoreactivity for LIF was absent throughout BCC and SCC, however, normal epidermis surrounding the tumour stained positive, as in normal skin. These data may suggest a role for LIF and IL-8 in the development of skin carcinomas, but without co-ordinate regulation of these two cytokines in this process.

The purpose of this note is to examine incumbent behaviour and patterns of entry under R&D competition with spillovers. We find that, in addition to blockading, deterring and accommodating entry, the incumbent may also solicit entry. Entry solicitation occurs when the incumbent strategically alters its R&D commitment in order to take advantage of the spillover generated by the entrant's subsequent R&D investment. Although our results are placed in the context of R&D with spillovers, they are applicable to a wider class of models involving positive externalities, particularly network externalities. JEL Classification Numbers: L12, O31.

kappa-Conotoxin PVIIA (kappa-PVIIA), a 27-amino acid toxin from Conus purpurascens venom that inhibits the Shaker potassium channel, was chemically synthesized in a biologically active form. The disulfide connectivity of the peptide was determined. kappa-Conotoxin PVIIA has the following structure. This is the first Conus peptide known to target K+ channels. [structure: see text] Although the Shaker K+ channel is sensitive to kappa-PVIIA, the rat brain Kv1.1 subtype is resistant. Chimeras between Shaker and the Kv1.1 K+ channels were constructed and expressed in Xenopus oocytes. Only channels containing the putative pore-forming region between the fifth and sixth transmembrane domains of Shaker retained toxin sensitivity, indicating that the toxin target site is in this region of the channel. Evidence is presented that kappa-PVIIA interacts with the external tetraethyl-ammonium binding site on the Shaker channel. Although both kappa-PVIIA and charybdotoxin inhibit the Shaker channel, they must interact differently. The F425G Shaker mutation increases charybdotoxin affinity by 3 orders of magnitude but abolishes kappa-PVIIA sensitivity. The precursor sequence of kappa-PVIIA was deduced from a cDNA clone, revealing a prepropeptide comprising 72 amino acids. The N-terminal region of the kappa-PVIIA prepropeptide exhibits striking homology to the omega-, muO-, and delta-conotoxins. Thus, at least four pharmacologically distinct superfamilies of Conus peptides belong to the same "O" superfamily, with the omega- and kappa-conotoxins forming one branch, and the delta- and muO-conotoxins forming a second major branch.

It has been suggested that leukaemia inhibitory factor (LIF), may be involved in the pathogenesis of cutaneous inflammation. In 5 patients with previously proven contact allergy to nickel, LIF mRNA and protein expression were assessed by reverse transcription-polymerase chain reaction and immunohistochemistry in 5% nickel sulfate patch test biopsies 24 h after application of the patch. Control specimens were obtained from non-tested and vehicle-tested skin from the same individuals. LIF mRNA expression was significantly increased in nickel-tested skin compared with both vehicle-tested (p = 0.045) and non-tested skin (p = 0.041). All biopsies showed similar patterns of LIF immunoreactivity, with no significant differences between nickel-tested, vehicle-tested and non-tested skin. Immunostaining was cytoplasmic and was present in the epidermis and hair follicles. No dermal staining was observed. This study suggests that LIF may play a role in the early phase of allergic contact dermatitis.

From February 1, 2000, to December 4, 2001, a total of 119 bats (85 Megachiroptera and 34 Microchiroptera) were tested for Australian bat lyssavirus (ABLV) infection. Eight Megachiroptera were positive by immunofluorescence assay that used cross-reactive antibodies to rabies nucleocapsid protein. A case study of cross-species transmission of ABLV supports the conclusion that a bat reservoir exists for ABLV in which the virus circulates across Megachiroptera species within mixed communities.

The US Coast Guard, US Navy and other maritime and port security units routinely conduct undersea inspections for a variety of mission requirements. However, current inspection techniques only sample a small number of vessels transiting into US waters, resulting in limited situational awareness in the undersea domain and creating an opportunity for introduction of threatening devices into harbors where they can inflict great harm. The Naval Undersea Warfare Center (NUWC) Detachment San Diego, NUWC Division Newport, and Battelle have developed and demonstrated undersea systems that can be combined to address several of these mission requirements in a joint deployment, facilitating more efficient and complete harbor security. This paper will provide an overview of each system component, including hardware descriptions and test results to date, and discuss deployment Concept of Operations (CONOPS) at a candidate location.