Gas chromatographic isolation of individual compounds from complex matrices for radiocarbon dating

This paper describes the application of a novel, practical approach for isolation of individual compounds from complex organic matrices for natural abundance radiocarbon measurement. This is achieved through the use of automated preparative capillary gas chromatography (PCGC) to separate and recover sufficient quantities of individual target compounds for C-14 analysis by accelerator mass spectrometry (AMS). We developed and tested this approach using a suite of samples (plant lipids, petroleums) whose ages spanned the C-14 time scale and which contained a variety of compound types (fatty acids, sterols, hydrocarbons), Comparison of individual compound and bulk radiocarbon signatures for the isotopically homogeneous samples studied revealed that Delta(14)C values generally agreed well (+/- 10%). Background contamination was assessed at each stage of the isolation procedure, and incomplete solvent removal prior to combustion was the only significant source of additional carbon, Isotope fractionation was addressed through compound-specific stable carbon isotopic analyses, Fractionation of isotopes during isolation of individual compounds was minimal (\u3c 5 parts per thousand for delta(13)C), provided the entire peak was collected during PCGC, Trapping of partially coeluting peaks did cause errors, and these results highlight the importance of conducting stable carbon isotopic measurements of each trapped compound in concert with AMS for reliable radiocarbon measurements, The addition of carbon accompanying derivatization of functionalized compounds (e.g., fatty acids and sterols) prior to chromatographic separation represents a further source of potential error, This contribution can be removed using a simple isotopic mass balance approach, Based on these preliminary results, the PCGC-based approach holds promise for accurately determining C-14 ages on compounds specific to a given source within complex, heterogeneous samples

Editorial

Editoria

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Incoherent non-Fermi liquid scattering in a Kondo lattice

One of the most notorious non-Fermi liquid properties of both archetypal heavy-fermion systems [1-4] and the high-Tc copper oxide superconductors [5] is an electrical resistivity that evolves linearly with temperature, T. In the heavy-fermion superconductor CeCoIn5 [5], this linear behaviour was one of the first indications of the presence of a zero-temperature instability, or quantum critical point. Here, we report the observation of a unique control parameter of T-linear scattering in CeCoIn5, found through systematic chemical substitutions of both magnetic and non-magnetic rare-earth, R, ions into the Ce sub-lattice. We find that the evolution of inelastic scattering in Ce1-xRxCoIn5 is strongly dependent on the f-electron configuration of the R ion, whereas two other key properties -- Cooper-pair breaking and Kondo-lattice coherence -- are not. Thus, T-linear resistivity in CeCoIn5 is intimately related to the nature of incoherent scattering centers in the Kondo lattice, which provides insight into the anomalous scattering rate synonymous with quantum criticality [7].Comment: 4 pages, 3 figures (published version

Switching of magnetic domains reveals evidence for spatially inhomogeneous superconductivity

The interplay of magnetic and charge fluctuations can lead to quantum phases with exceptional electronic properties. A case in point is magnetically-driven superconductivity, where magnetic correlations fundamentally affect the underlying symmetry and generate new physical properties. The superconducting wave-function in most known magnetic superconductors does not break translational symmetry. However, it has been predicted that modulated triplet p-wave superconductivity occurs in singlet d-wave superconductors with spin-density wave (SDW) order. Here we report evidence for the presence of a spatially inhomogeneous p-wave Cooper pair-density wave (PDW) in CeCoIn5. We show that the SDW domains can be switched completely by a tiny change of the magnetic field direction, which is naturally explained by the presence of triplet superconductivity. Further, the Q-phase emerges in a common magneto-superconducting quantum critical point. The Q-phase of CeCoIn5 thus represents an example where spatially modulated superconductivity is associated with SDW order

Hemostasis and ageing

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role

The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia

BACKGROUND: Recent studies suggest that HMG-CoA reductase inhibitors ("statins") may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of statins on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk based on the pneumonia severity index. In the multivariable regression analysis, after adjusting for potential confounders including a propensity score, the use of statins at presentation (odds ratio 0.36, 95% confidence interval 0.14–0.92) was associated with decreased 30-day mortality. DISCUSSION: Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

INTRODUCTION: Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. METHODS AND RESULTS: Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. CONCLUSION: Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline