Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis.

Recent studies have established cell type- specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-kappaB. In each of these studies, inhibitors of NF-kappaB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To address whether Sindbis virus- induced NF-kappaB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-kappaB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-kappaB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-kappaB activity relative to the death stimulus

Vitamin C inhibits endothelial cell apoptosis in congestive heart failure

Background - Proinflammatory cytokines like tumor necrosis factor- and oxidative stress induce apoptotic cell death in endothelial cells (ECs). Systemic inflammation and increased oxidative stress in congestive heart failure (CHF) coincide with enhanced EC apoptosis and the development of endothelial dysfunction. Therefore, we investigated the effects of antioxidative vitamin C therapy on EC apoptosis in CHF patients. Methods and Results - Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor- and angiotensin II in vitro as assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32±8% of baseline levels, whereas placebo had no effect (87±14%, P<0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients (P<0.001). Conclusions - Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function

Effective Conformal Theory and the Flat-Space Limit of AdS

We develop the idea of an effective conformal theory describing the low-lying spectrum of the dilatation operator in a CFT. Such an effective theory is useful when the spectrum contains a hierarchy in the dimension of operators, and a small parameter whose role is similar to that of 1/N in a large N gauge theory. These criteria insure that there is a regime where the dilatation operator is modified perturbatively. Global AdS is the natural framework for perturbations of the dilatation operator respecting conformal invariance, much as Minkowski space naturally describes Lorentz invariant perturbations of the Hamiltonian. Assuming that the lowest-dimension single-trace operator is a scalar, O, we consider the anomalous dimensions, gamma(n,l), of the double-trace operators of the form O (del^2)^n (del)^l O. Purely from the CFT we find that perturbative unitarity places a bound on these dimensions of |gamma(n,l)|<4. Non-renormalizable AdS interactions lead to violations of the bound at large values of n. We also consider the case that these interactions are generated by integrating out a heavy scalar field in AdS. We show that the presence of the heavy field "unitarizes" the growth in the anomalous dimensions, and leads to a resonance-like behavior in gamma(n,l) when n is close to the dimension of the CFT operator dual to the heavy field. Finally, we demonstrate that bulk flat-space S-matrix elements can be extracted from the large n behavior of the anomalous dimensions. This leads to a direct connection between the spectrum of anomalous dimensions in d-dimensional CFTs and flat-space S-matrix elements in d+1 dimensions. We comment on the emergence of flat-space locality from the CFT perspective.Comment: 46 pages, 2 figures. v2: JHEP published versio

A core Outcome Set for Seamless, Standardized Evaluation of Innovative Surgical Procedures and Devices (COHESIVE)

OBJECTIVE: To develop a core outcome set (COS), an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques. SUMMARY BACKGROUND DATA: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. METHODS: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. RESULTS: 7,972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. 410 international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. 12 outcomes were scored ‘consensus in’ (‘very important’ by ≥70% of patients and professionals) and 20 ‘no consensus’. A consensus meeting, involving 19 professionals and 10 patient/public representatives, led to agreement on a final 8-domain COS. Six domains are specific to a surgical innovation context: modifications, unexpected disadvantages, device problems, technical procedure success, whether the overall desired effect was achieved, surgeons’/operators’ experience. Two domains relate to intended benefits and expected disadvantages. CONCLUSIONS: The COS is recommended for use in all studies prior to definitive RCT evaluation to promote safe, transparent, and efficient surgical innovation

Environmental and effluent monitoring at ANSTO sites, 2002-2003.

This report presents the results of environmental and effluent monitoring at the Lucas Heights Science and Technology Centre (LHSTC) and the National Medical Cyclotron (NMC) from January 2002 to June 2003. Potential effective dose rates to the general public from airborne discharges from the LHSTC site were less than 0.01 mSv/year, well below the 1 mSv/year dose rate limit for long term exposure that is recommended by the Australian National Occupational Health and Safety Commission. The effective dose rates to hypothetical individuals potentially exposed to radiation in routine liquid effluent discharges from the LHSTC were recently calculated to be less than 0.001 mSv/year. This is much less than dose rates estimated for members of public potentially exposed to airborne emissions. The levels of tritium detected in groundwater and stormwater at the LHSTC were less than the Australian drinking water guidelines. The airborne and liquid effluent emissions from the NMC were below the ARPANSA-approved notification levels and NSW EPA limits, respectively. ANSTO's routine operations at the LHSTC and the NMC make only a very small addition to the natural background radiation dose experienced by members of the Australian public

Environmental and effluent monitoring at ANSTO sites, 2006-2007.

This report presents the results of ANSTO’s environmental and effluent monitoring at the Lucas Heights Science and Technology Centre (LHSTC) and the National Medical Cyclotron (NMC) sites, from July 2006 to June 2007. Estimated effective doses to the members of the public potentially affected by routine airborne emissions from the LHSTC were lower than in previous years due to the closure of the HIFAR research reactor. The maximum potential off-site dose of 0.002 mSv/year was 10% of the As Low As Reasonably Achievable (ALARA) objective of 0.02 mSv/year, and much lower than the public dose limit of 1 mSv/year that is recommended by the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). The effective doses to the critical group potentially exposed to routine liquid effluent releases from the LHSTC have been realistically assessed at less than 25% of the estimated doses to the critical group for airborne releases. Based on releases of liquid effluent from the LHSTC during 2006-07, a radiological risk assessment was conducted for marine biota in the receiving environment at Potter Point. The possible dose-rates to various species of marine biota were evaluated against international criteria recommended for the protection of biota from radiological hazards. In all cases it was concluded that the radiological risk to marine biota from ANSTO’s effluent releases was negligible. The median tritium concentrations detected in groundwater and surface waters at the LHSTC were typically less than 2% of those set out in the Australian Drinking Water Guidelines. The airborne emissions from the NMC were below the ARPANSA-approved notification levels. Results of environmental monitoring at both ANSTO sites confirm that the facilities continue to be operated well within regulatory limits. ANSTO’s routine operations at the LHSTC and NMC make only a very small addition to the natural background radiation dose of approximately 1.5 mSv/year experienced by members of the Australian public

Garside and quadratic normalisation: a survey

Starting from the seminal example of the greedy normal norm in braid monoids, we analyse the mechanism of the normal form in a Garside monoid and explain how it extends to the more general framework of Garside families. Extending the viewpoint even more, we then consider general quadratic normalisation procedures and characterise Garside normalisation among them.Comment: 30 page

Environmental and effluent monitoring at ANSTO sites, 2005-2006.

This report presents the results of ANSTO's environmental and effluent monitoring at Lucas Heights Science and Technology Centre (LHSTC) and the National Medical Cyclotron (NMC) sites, from July 2005 to June 2006. Estimated effective doses to the critical group of members of the public potentially affected by routine airborne emissions from the LHSTC were less that 0.005 mSv/year. The maximum potential dose was 23% of the ANSTO ALARA objective of 0.02 mSv/year, much lower than the public dose limit of 1mSv/year that is recommended by the Australian Radiation Protection and Nuclear Safety Authority (ARPANSA). The effective doses to the critical groups of members of the public potentially exposed to routine liquid effluent releases from the LHSTC have been realistically estimated as a quarter (or less) of the estimated doses to the critical group for airborne releases. The medium tritium concentrations detected in groundwater and surface waters at the LHSTC were typically less than 2% of those set out in the Australian Drinking Water Guidelines. The airborne emissions from the NMC were below the ARPANSA-approved notification levels. Results of environmental monitoring at both ANSTO sites confirm that the facilities continue to be operated well within regulatory limits. ANSTO's routine operations at the LHSTC and NMC make only a very small addition to the natural background radiation dose of ~1.5 mSv/year experienced by members of the Australian public

Environmental and effluent monitoring at ANSTO sites: 2003-2004.

This report presents the results of ANSTO's environmental and effluent monitoring at the Lucas Heights Science and Technology Centre (LHSTC) and the National Medical Cyclotron (NMC) sites, from July 2003 to June 2004. Effective doses to the critical group of members of the public potentially affected by routine airborne emissions from the LHSTC were less than 0.004 mSv/year. This estimated maximum potential dose is less than 20% of the ANSTO ALARA objective of 0.02 mSv/year and much lower than the public dose limit of 1 mSv/year that is recommended by the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). The effective doses to the critical group of members of the public potentially exposed to routine liquid effluent releases from the LHSTC have been realistically estimated as a quarter (or less) of the estimated doses to the critical group for airborne releases. The levels of tritium detected in groundwater and stormwater at the LHSTC were less than the Australian Drinking Water Guidelines. The airborne and liquid effluent emissions from the NMC were below the ARPANSA-approved notification levels and NSW Department of Environment and Conservation limits, respectively. Results of environmental monitoring at both ANSTO sites confirm that the facilities continue to be operated well within regulatory limits. Members of the public are exposed to only very small doses of radiation from ANSTO's routine airborne and liquid effluent releases

Environmental and effluent monitoring at ANSTO sites, 2004-2005.

This report presents the results of ANSTO's environmental and effluent monitoring at the Lucas Heights Science and Technology Centre (LHSTC) and the National Medical Cyclotron (NMC) sites, from July 2004 to June 2005. Effective doses to the critical group of members of the public potentially affected by routine airborne emissions from the LHSTC were less than 0.005 mSv/year. This estimated maximum potential dose is less than 24% of the ANSTO ALARA objective of 0.02 mSv/year, and much lower than the public dose limit of 1 mSv/year that is recommended by the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). The effective doses to the critical group of members of the public potentially exposed to routine liquid effluent releases from the LHSTC have been realistically estimated as a quarter (or less) of the estimated doses to the critical group for airborne releases. The levels of tritium detected in groundwater and stormwater at the LHSTC were less than those set out in the Australian Drinking Water Guidelines. The airborne and liquid effluent emissions from the NMC were below both the ARPANSA-approved notification levels and Sydney Water limits for acceptance of trade wastewater to sewer. Results of environmental monitoring at both ANSTO sites confirm that the facilities continue to be operated well within regulatory limits. ANSTO's routine operations at the LHSTC and NMC make only a very small addition to the natural background radiation dose of ~1.5 mSv/year experienced by members of the Australian public