Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe hepatic encephalopathy

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral haemodynamics. Six successive patients with ALF were electively ventilated for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety- Schmidt technique). Measurements were made before, at 1, 3 hour and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg) )intravenously (single bolus), median 0.25mg (range 0.2-0.3). There was no significant change in heart rate, mean arterial pressure or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (p<0.0=0.016) respectively. Intracranial pressure increased significantly at 21 hours (p<0=.0.031), returning back to baseline values at 42 hours. This study shows that administration of terlipressin, at a dose that did not alter systemic haemodynamicshemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral haemodynamics

On the Influence of Stochastic Moments in the Solution of the Neutron Point Kinetics Equation

On the Influence of Stochastic Moments in the Solution of the Neutron Point Kinetics EquationComment: 12 pages, 2 figure

Theoretical Evaluations of the Fission Cross Section of the 77 eV Isomer of 235-U

We have developed models of the fission barrier (barrier heights and transition state spectra) that reproduce reasonably well the measured fission cross section of $^{235}$U from neutron energy of 1 keV to 2 MeV. From these models we have calculated the fission cross section of the 77 eV isomer of $^{235}$U over the same energy range. We find that the ratio of the isomer cross section to that of the ground state lies between about 0.45 and 0.55 at low neutron energies. The cross sections become approximately equal above 1 MeV. The ratio of the neutron capture cross section to the fission cross section for the isomer is predicted to be about a factor of 3 larger for the isomer than for the ground state of $^{235}$U at keV neutron energies. We have also calculated the cross section for the population of the isomer by inelastic neutron scattering form the $^{235}$U ground state. We find that the isomer is strongly populated, and for $E_n = 1 MeV$ the $(n,n'\gamma)$ cross section leading to the population of the isomer is of the order of 0.5 barn. Thus, neutron reaction network calculations involving the uranium isotopes in a high neutron fluence are likely to be affected by the 77 eV isomer of $^{235}$U. With these same models the fission cross sections of $^{233}$U and $^{237}$U can be reproduced approximately using only minor adjustments to the barrier heights. With the significant lowering of the outer barrier that is expected for the outer barrier the general behavior of the fission cross section of $^{239}$Pu can also be reproduced.Comment: 17 pages including 8 figure

Gender moderates the relationship between empathy and aggressiveness in sport: The mediating role of anger

This research investigated whether gender moderates, and anger mediates, the relationship between empathy (i.e., perspective taking and empathic concern) and aggressiveness in sport. In Study 1, perspective taking and empathic concern were negatively associated with aggressiveness, and this effect was stronger in women compared to men. In Study 2, perspective taking was a negative predictor of aggressiveness and antisocial behavior in sport, and anger mediated these relationships in women, but not in men. Our findings suggest that empathy and emotion-based strategies targeted at reducing aggressiveness in sport need to be tailored for males and females

Evolution of a Holocene delta driven by episodic sediment delivery and coseismic deformation, Puget Sound, Washington, USA

This paper is not subject to U.S. copyright. The definitive version was published in Sedimentology 53 (2006): 1211-1228, doi:10.1111/j.1365-3091.2006.00809.x.Episodic, large-volume pulses of volcaniclastic sediment and coseismic subsidence of the coast have influenced the development of a late Holocene delta at southern Puget Sound. Multibeam bathymetry, ground-penetrating radar (GPR) and vibracores were used to investigate the morphologic and stratigraphic evolution of the Nisqually River delta. Two fluvial–deltaic facies are recognized on the basis of GPR data and sedimentary characteristics in cores, which suggest partial emplacement from sediment-rich floods that originated on Mount Rainier. Facies S consists of stacked, sheet-like deposits of andesitic sand up to 4 m thick that are continuous across the entire width of the delta. Flat-lying, highly reflective surfaces separate the sand sheets and comprise important facies boundaries. Beds of massive, pumice- and charcoal-rich sand overlie one of the buried surfaces. Organic-rich material from that surface, beneath the massive sand, yielded a radiocarbon age that is time-correlative with a series of known eruptive events that generated lahars in the upper Nisqually River valley. Facies CF consists of linear sandbodies or palaeochannels incised into facies S on the lower delta plain. Radiocarbon ages of wood fragments in the sandy channel-fill deposits also correlate in time to lahar deposits in upstream areas. Intrusive, sand-filled dikes and sills indicate liquefaction caused by post-depositional ground shaking related to earthquakes. Continued progradation of the delta into Puget Sound is currently balanced by tidal-current reworking, which redistributes sediment into large fields of ebb- and flood-oriented bedforms.This study was supported by the Coastal and Marine Geology Program, and the Earthquake Hazards Program of the U.S. Geological Survey

The prognostic significance of low-frequency somatic mutations in metastatic cutaneous melanoma

Background: Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance. Methods: After limiting our DNA sequencing analysis to MM samples (n = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF). We performed Cox analysis on 53 genes that were mutated in ≥3% of samples, and had ≥50% difference in incidence of mutations in deceased subjects versus alive subjects. Results: Four genes were potentially prognostic [RAC1, FGFR1, CARD11, CIITA; false discovery rate (FDR) 75% of the samples that exhibited corresponding DNA mutations. The low frequency, UV signature type and RNA expression of the 22 genes in MM samples were confirmed in a separate multi-institution validation cohort (n = 413). An underpowered analysis within a subset of this validation cohort with available patient follow-up (n = 224) showed that somatic mutations in SPEN and RAC1 reached borderline prognostic significance [log-rank favorable (p = 0.09) and adverse (p = 0.07), respectively]. Somatic mutations in SPEN, and to a lesser extent RAC1, were not associated with definite gene copy number or RNA expression alterations. High (>2+) nuclear plus cytoplasmic expression intensity for SPEN was associated with longer melanoma-specific overall survival (OS) compared to lower (≤ 2+) nuclear intensity (p = 0.048). We conclude that expressed somatic mutations in infrequently mutated genes beyond the well-characterized ones (e.g., BRAF, RAS, CDKN2A, PTEN, TP53), such as RAC1 and SPEN, may have prognostic significance in MM

Ripples in a pond: Do social work students need to learn about terrorism?

In the face of heightened awareness of terrorism, however it is defined, the challenges for social work are legion. Social work roles may include working with the military to ensure the well-being of service-men and women and their families when bereaved or injured, as well as being prepared to support the public within the emergency context of an overt act of terrorism. This paper reviews some of the literature concerning how social work responds to confl ict and terrorism before reporting a smallscale qualitative study examining the views of social work students, on a qualifying programme in the UK, of terrorism and the need for knowledge and understanding as part of their education

Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone

The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long-term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor-intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone-metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune-based therapies in solid cancers.Katie L Owen, Linden J Gearing, Damien J Zanker, Natasha K Brockwell, Weng Hua Khoo, Daniel L Roden, Marek Cmero, Stefano Mangiola, Matthew K Hong, Alex J Spurling, Michelle McDonald, Chia-Ling Chan, Anupama Pasam, Ruth J Lyons, Hendrika M Duivenvoorden, Andrew Ryan, Lisa M Butler, John M Mariadason, Tri Giang Phan, Vanessa M Hayes, Shahneen Sandhu, Alexander Swarbrick, Niall M Corcoran, Paul J Hertzog, Peter I Croucher, Chris Hovens, Belinda S Parke