Observational Constraints on General Relativistic Energy Conditions, Cosmic Matter Density and Dark Energy from X-Ray Clusters of Galaxies and Type-Ia Supernovae

New observational constraints on the cosmic matter density $\Omega_m$ and an effectively redshift-independent equation of state parameter $w_x$ of the dark energy are obtained while simultaneously testing the strong and null energy conditions of general relativity on macroscopic scales. The combination of REFLEX X-ray cluster and type-Ia supernova data shows that for a flat Universe the strong energy condition might presently be violated whereas the null energy condition seems to be fulfilled. This provides another observational argument for the present accelerated cosmic expansion and the absence of exotic physical phenomena related to a broken null energy condition. The marginalization of the likelihood distributions is performed in a manner to include a large fraction of the recently discussed possible systematic errors involved in the application of X-ray clusters as cosmological probes. This yields for a flat Universe, $\Omega_m=0.29^{+0.08}_{-0.12}$ and $w_x=-0.95^{+0.30}_{-0.35}$ ($1\sigma$ errors without cosmic variance). The scatter in the different analyses indicates a quite robust result around $w_x=-1$, leaving little room for the introduction of new energy components described by quintessence-like models or phantom energy. The most natural interpretation of the data is a positive cosmological constant with $w_x=-1 or something like it.Comment: 11 pages, 5 figures, Astron. Astrophys. (in press

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study11The data reported here were supplied by the United States Renal Data System. Interpretation of these data is the responsibility of the authors, and in no way should be seen as an official policy or interpretation of the U.S. government.

Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study.BackgroundThe long-term prognostic associations of pre- and post-dialysis blood pressures, interdialytic weight gain, and antihypertensive use in hemodialysis patients are unclear.MethodsThe United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Waves 3 and 4 Study, a randomly generated sample of 11,142 subjects receiving hemodialysis on December 31, 1993, was examined, with vital status followed until May 2000.ResultsPre- and post-dialysis blood pressure values, interdialytic weight gain and number of antihypertensives averaged 151.8/79.7, 137.0/74, 3.6% and 0.76, respectively. Prognostic discrimination was maximized by considering pre- and post-systolic and diastolic blood pressure values simultaneously, in a pattern suggesting that wide pulse pressures were associated with mortality (P < 0.0001). Comorbidity adjustment markedly affected associations, with low pre-dialysis diastolic (P < 0.05), low post-dialysis dialysis diastolic pressure (P < 0.05), high post-dialysis dialysis systolic pressure (P < 0.05), and high interdialytic weight gains (P = 0.005) associated with mortality. Each class of antihypertensive drug, except angiotensin-converting enzyme (ACE)-inhibitors, was associated with lower mortality in unadjusted models, an effect most pronounced for beta-blockers (hazards ratio 0.72, 95% CI 0.66 to 0.79, P < 0.0001). Comorbidity adjustment eliminated survival associations for each antihypertensive class except beta-blockers.ConclusionsPre- and post-dialysis blood pressure values have independent associations with mortality, in a way that implicates wide pulse pressures. Much of the adverse prognosis of wide pulse pressures probably reflects older age and cardiovascular comorbidity. Large interdialytic weight gains are associated with shorter survival when comorbidity is taken into account. Beta-blocker use shows a robust association with survival, and may be protective

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis

The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis.BackgroundWhile the survival ramifications of dialysis modality selection are still debated, it seems reasonable to postulate that outcome comparisons are not the same for all patients at all times. Trends in available data indicate the relative risk of death with hemodialysis (HD) compared to peritoneal dialysis (PD) varies by time on dialysis and the presence of various risk factors. This study was undertaken to identify key patient characteristics for which the risk of death differs by dialysis modality.MethodsAnalyses utilized incidence data from 398,940 United States Medicare patients initiating dialysis between 1995 and 2000. Proportional hazards regression identified the presence of diabetes, age, and the presence of comorbidity as factors that significantly interact with treatment modality. Stratifying by these factors, proportional and nonproportional hazards models were used to estimate relative risks of death [RR (HD:PD)].ResultsOf the 398,940 patients studied, 11.6% used PD as initial therapy, 45% had diabetes mellitus (DM), 51% were 65 years or older, and 55% had at least one comorbidity. Among the 178,693 (45%) patients with no baseline comorbidity, adjusted mortality rates in nondiabetic (non-DM) patients were significantly higher on HD than on PD [age 18–44: RR (95% CI) = 1.24 (1.07, 1.44); age 45–64: RR = 1.13 (1.02, 1.25); age 65+: RR = 1.13 (1.05, 1.21)]. Among diabetic (DM) patients with no comorbidity, HD was associated with a higher risk of death among younger patients [age 18–44: RR = 1.22(1.05, 1.42)] and a lower risk of death among older patients [age 45–64: RR = 0.92 (0.85, 1.00); age 65+: RR = 0.86 (0.79, 0.93)]. Within the group of 220,247 (55%) patients with baseline comorbidity, adjusted mortality rates were not different between HD and PD among non-DM patients [age 18–44: RR = 1.19 (0.94, 1.50); age 45–64: RR = 1.01 (0.92, 1.11); age 65+: RR = 0.96 (0.91, 1.01)] and younger DM patients [age 18–44: RR = 1.10 (0.92, 1.32)], but were lower with HD among older DM patients with baseline comorbidity [age 45–64: RR = 0.82 (0.77, 0.87); age 65+: RR = 0.80 (0.76, 0.85)].ConclusionValid mortality comparisons between HD and PD require patient stratification according to major risk factors known to interact with treatment modality. Survival differences between HD and PD are not constant, but vary substantially according to the underlying cause of ESRD, age, and level of baseline comorbidity. These results may help identify technical advances that will improve outcomes of patients on dialysis

An analysis of trends, frequencies and factors influencing the development of resistance to phosphine in the red flour beetle Tribolium castaneum (Herbst) in Australia

Although resistance to phosphine, the key disinfestant used worldwide in the stored grain environment has been an ongoing industry issue, studies on its trend over large geographic region and over long period of time is very limited. In this study, we critically analysed 20 years' phosphine resistance diagnosis data for the red flour beetle Tribolium castaneum (Herbst) stored in the Australian Grain Insect Resistance Database. Resistance diagnosis on a staggering 6336 samples, along with information on storage types and treatment history was interrogated to establish trends and frequencies of resistance development in this species and factors that may have contributed towards these resistance occurences. Using descriptive statistics, linear and trend analysis and a well established Bayesian hurdle model, we determined that strong resistance in T. castaneum was significantly more prevalent in quarantine intereceptions than in central storages and on farms. The strong resistance incidences had been confined to eastern states of Queensland, New South Wales, Victoria and South Australia, whereas it is yet to be detected in the state of Western Australia. We could not establish any significant correlation between the strong resistance development and any commodity or treatments. After an initial increasing trend in incidences since the first detection of strong resistance in 1997 in this species, the frequency was stabilised during 2001–08; after which there had been an upward trend since 2009 till the last survey in 2013. The conclusions derived from this analyses highlighted the importance of a resistance monitoring program with relevant information being used in Australia as the basis for ongoing and future phosphine resistance management strategies. This research may also proved valuable towards devising similar strategies in overseas countries with phosphine resistance problems

Targeted Transcriptomics of Frog Virus 3 in Infected Frog Tissues Reveal Non-Coding Regulatory Elements and microRNAs in the Ranaviral Genome and Their Potential Interaction with Host Immune Response

Background: Frog Virus 3 (FV3) is a large dsDNA virus belonging to Ranaviruses of family Iridoviridae. Ranaviruses infect cold-blood vertebrates including amphibians, fish and reptiles, and contribute to catastrophic amphibian declines. FV3 has a genome at ~105 kb that contains nearly 100 coding genes and 50 intergenic regions as annotated in its reference genome. Previous studies have mainly focused on coding genes and rarely addressed potential non-coding regulatory role of intergenic regions. Results: Using a whole transcriptomic analysis of total RNA samples containing both the viral and cellular transcripts from FV3-infected frog tissues, we detected virus-specific reads mapping in non-coding intergenic regions, in addition to reads from coding genes. Further analyses identified multiple cis-regulatory elements (CREs) in intergenic regions neighboring highly transcribed coding genes. These CREs include not only a virus TATA-Box present in FV3 core promoters as in eukaryotic genes, but also viral mimics of CREs interacting with several transcription factors including CEBPs, CREBs, IRFs, NF-κB, and STATs, which are critical for regulation of cellular immunity and cytokine responses. Our study suggests that intergenic regions immediately upstream of highly expressed FV3 genes have evolved to bind IRFs, NF-κB, and STATs more efficiently. Moreover, we found an enrichment of putative microRNA (miRNA) sequences in more than five intergenic regions of the FV3 genome. Our sequence analysis indicates that a fraction of these viral miRNAs is targeting the 3’-UTR regions of Xenopus genes involved in interferon (IFN)-dependent responses, including particularly those encoding IFN receptor subunits and IFN-regulatory factors (IRFs). Conclusions: Using the FV3 model, this study provides a first genome-wide analysis of non-coding regulatory mechanisms adopted by ranaviruses to epigenetically regulate both viral and host gene expressions, which have co-evolved to interact especially with the host IFN response

Virus-Targeted Transcriptomic Analyses Implicate Ranaviral Interaction with Host Interferon Response in Frog Virus 3-Infected Frog Tissues

Ranaviruses (Iridoviridae), including Frog Virus 3 (FV3), are large dsDNA viruses that cause devastating infections globally in amphibians, fish, and reptiles, and contribute to catastrophic amphibian declines. FV3’s large genome (~105 kb) contains at least 98 putative open reading frames (ORFs) as annotated in its reference genome. Previous studies have classified these coding genes into temporal classes as immediate early, delayed early, and late viral transcripts based on their sequential expression during FV3 infection. To establish a high-throughput characterization of ranaviral gene expression at the genome scale, we performed a whole transcriptomic analysis (RNA-Seq) using total RNA samples containing both viral and cellular transcripts from FV3-infected Xenopus laevis adult tissues using two FV3 strains, a wild type (FV3-WT) and an ORF64R-deleted recombinant (FV3-∆64R). In samples from the infected intestine, liver, spleen, lung, and especially kidney, an FV3-targeted transcriptomic analysis mapped reads spanning the full-genome coverage at ~10× depth on both positive and negative strands. By contrast, reads were only mapped to partial genomic regions in samples from the infected thymus, skin, and muscle. Extensive analyses validated the expression of almost all of the 98 annotated ORFs and profiled their differential expression in a tissue-, virus-, and temporal class-dependent manner. Further studies identified several putative ORFs that encode hypothetical proteins containing viral mimicking conserved domains found in host interferon (IFN) regulatory factors (IRFs) and IFN receptors. This study provides the first comprehensive genome-wide viral transcriptome profiling during infection and across multiple amphibian host tissues that will serve as an instrumental reference. Our findings imply that Ranaviruses like FV3 have acquired previously unknown molecular mimics, interfering with host IFN signaling during evolution

Dynamic Fracture and Crack Arrest Toughness Evaluation of High-Performance Steel Used in Highway Bridges

Impact energy tests are an efficient method of verifying adequate toughness of steel prior to it being put into service. Based on a multitude of historical correlations between impact energy and fracture toughness, minimum impact energy requirements that correspond to desired levels of fracture toughness are prescribed by steel bridge design specifications. Research characterizing the fracture behavior of grade 485 and 690 (70 and 100) high-performance steel utilized impact, fracture toughness, and crack arrest testing to verify adequate performance for bridge applications. Fracture toughness results from both quasi-static and dynamic stress intensity rate tests were analyzed using the most recently adopted master curve methodology. Both impact and fracture toughness tests indicated performance significantly greater than the minimum required by material specifications. Even at the AASHTO Zone III service temperature, which is significantly colder than prescribed test temperatures, minimum average impact energy requirements were greatly exceeded. All master curve reference temperatures, both for quasi-static and dynamic loading rates, were found to be colder than the Zone III minimum service temperature. Three correlations between impact energy and fracture toughness were evaluated and found to estimate reference temperatures that are conservative by 12 to 50 °C (22 to 90 °F) on average for the grades and specimen types tested. The evaluation of two reference temperature shifts intended to account for the loading rate was also performed and the results are discussed

A non-synonymous polymorphism in IL-23R Gene (rs1884444) is associated with reduced risk to schistosomiasis-associated Immune Reconstitution Inflammatory Syndrome in a Kenyan population

BACKGROUND: Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya. About 36% of this population initiating antiretroviral therapy (ART) experience Immune Reconstitution Inflammatory Syndrome (IRIS) that complicates recovery. Several IL-23R alleles have been associated with susceptibility to both autoimmune and inflammatory diseases through T-helper type 17 (TH(17)) cells. However, whether or not variants within the IL-23R increase susceptibility to IRIS in western Kenya is unknown. The objective of the current study was to determine the association between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti-retroviral therapy (HAART). METHODS: A three-month case–control study was conducted on antiretroviral naïve schistosomiasis/HIV co-infected fishermen starting HAART in Uyoma Rarieda, Siaya County, Kenya. Seventy one patients were sampled at baseline and followed up for three months, to establish if they developed Schistosoma-related IRIS. In addition, the CD4+ cell counts and HIV RNA levels were determined in pre- and post-administration of HAART. Variations at five polymorphic sites of IL-23R (rs1884444, rs11465754, rs6682925, rs7530511 and rs7539625) based on >10% minor allele frequency in Yoruban reference population was determined using Allelic Discrimination Assay. The association between the five variants and susceptibility to IRIS was determined using logistic regression while controlling for potential confounders. In addition, the functional differences between the baseline CD4 + Cell counts and viral loads were determined using medians while across IL-23R genotypes were determined using Kruskal-Wallis tests. RESULTS: Overall, 26 (36.6%) patients developed schistosomiasis-associated IRIS at a median age of 35.5 years. Carriage of the TT genotype at the non-synonymous rs1884444 T > G relative to GG, was associated with a decreased risk of schistosomiasis-associated IRIS (OR, 0.25, 95% CI, 0.07-0.96, P = 0.043) while both baseline CD4+ cell counts and viral loads had no association with IRIS. CONCLUSION: These findings indicate that the non-synonymous variant rs1884444 T > G of IL-23R is associated with a decreased risk to schistosomiasis-associated IRIS. However, additional studies in a larger cohort and with an all inclusive polymorphic variants in the synonymous and non-synonymous regions need to be evaluated