Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.info:eu-repo/semantics/publishedVersio

Use of pepper spray in policing : retrospective study of situational characteristics and implications for violent situations

Pepper spray (OC) is a policing tool aimed to prevent or stop aggressive behavior by quickly and temporarily incapacitate without injuring. To date, few studies have investigated OC’s operational usefulness and limitations. OC reduced violent behavior in 93% of the 936 incidents investigated. However, the operative range was often <2 m and it took between 3 and 5 s of spraying before obtaining effect, partly owing to the difficulties of hitting a small, sometimes erratically moving target. Collateral hits were noted in 24% of the incidents, whereof 90% were other officers. Noteworthy, in 21% of incidents officers put themselves at large personal risk by using OC at close range against people armed with lethal weapons. Hence, OC emerges as a suitable tool for handling low threat situations but lacks key traits to ensure safe and efficient policing of high threat situations, e.g., handling armed assailants

A Nordic survey of CT doses in hybrid PET/CT and SPECT/CT examinations

Background Computed tomography (CT) scans are routinely performed in positron emission tomography (PET) and single photon emission computed tomography (SPECT) examinations globally, yet few surveys have been conducted to gather national diagnostic reference level (NDRL) data for CT radiation doses in positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT). In this first Nordic-wide study of CT doses in hybrid imaging, Nordic NDRL CT doses are suggested for PET/CT and SPECT/CT examinations specific to the clinical purpose of CT, and the scope for optimisation is evaluated. Data on hybrid imaging CT exposures and clinical purpose of CT were gathered for 5 PET/CT and 8 SPECT/CT examinations via designed booklet. For each included dataset for a given facility and scanner type, the computed tomography dose index by volume (CTDIvol) and dose length product (DLP) was interpolated for a 75-kg person (referred to as CTDIvol,75kg and DLP75kg). Suggested NDRL (75th percentile) and achievable doses (50th percentile) were determined for CTDIvol,75kg and DLP75kg according to clinical purpose of CT. Differences in maximum and minimum doses (derived for a 75-kg patient) between facilities were also calculated for each examination and clinical purpose. Results Data were processed from 83 scanners from 43 facilities. Data were sufficient to suggest Nordic NDRL CT doses for the following: PET/CT oncology (localisation/characterisation, 15 systems); infection/inflammation (localisation/characterisation, 13 systems); brain (attenuation correction (AC) only, 11 systems); cardiac PET/CT and SPECT/CT (AC only, 30 systems); SPECT/CT lung (localisation/characterisation, 12 systems); bone (localisation/characterisation, 30 systems); and parathyroid (localisation/characterisation, 13 systems). Great variations in dose were seen for all aforementioned examinations. Greatest differences in DLP75kg for each examination, specific to clinical purpose, were as follows: SPECT/CT lung AC only (27.4); PET/CT and SPECT/CT cardiac AC only (19.6); infection/inflammation AC only (18.1); PET/CT brain localisation/characterisation (16.8); SPECT/CT bone localisation/characterisation (10.0); PET/CT oncology AC only (9.0); and SPECT/CT parathyroid localisation/characterisation (7.8). Conclusions Suggested Nordic NDRL CT doses are presented according to clinical purpose of CT for PET/CT oncology, infection/inflammation, brain, PET/CT and SPECT/CT cardiac, and SPECT/CT lung, bone, and parathyroid. The large variation in doses suggests great scope for optimisation in all 8 examinations.Peer reviewe

The Amundsen Sea Polynya International Research Expedition (ASPIRE)

In search of an explanation for some of the greenest waters ever seen in coastal Antarctica and their possible link to some of the fastest melting glaciers and declining summer sea ice, the Amundsen Sea Polynya International Research Expedition (ASPIRE) challenged the capabilities of the US Antarctic Program and RVIB Nathaniel B. Palmer during Austral summer 2010–2011. We were well rewarded by both an extraordinary research platform and a truly remarkable oceanic setting. Here we provide further insights into the key questions that motivated our sampling approach during ASPIRE and present some preliminary findings, while highlighting the value of the Palmer for accomplishing complex, multifaceted oceanographic research in such a challenging environment

Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96). CONCLUSIONS: In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Improving simultaneous saccharification and co-fermentation of pretreated wheat straw using both enzyme and substrate feeding

<p>Abstract</p> <p>Background</p> <p>Simultaneous saccharification and co-fermentation (SSCF) has been recognized as a feasible option for ethanol production from xylose-rich lignocellulosic materials. To reach high ethanol concentration in the broth, a high content of water-insoluble solids (WIS) is needed, which creates mixing problems and, furthermore, may decrease xylose uptake. Feeding of substrate has already been proven to give a higher xylose conversion than a batch SSCF. In the current work, enzyme feeding, in addition to substrate feeding, was investigated as a means of enabling a higher WIS content with a high xylose conversion in SSCF of a xylose-rich material. A recombinant xylose-fermenting strain of <it>Saccharomyces cerevisiae </it>(TMB3400) was used for this purpose in fed-batch SSCF experiments of steam-pretreated wheat straw.</p> <p>Results</p> <p>By using both enzyme and substrate feeding, the xylose conversion in SSCF could be increased from 40% to 50% in comparison to substrate feeding only. In addition, by this design of the feeding strategy, it was possible to process a WIS content corresponding to 11% in SSCF and obtain an ethanol yield on fermentable sugars of 0.35 g g^-1.</p> <p>Conclusion</p> <p>A combination of enzyme and substrate feeding was shown to enhance xylose uptake by yeast and increase overall ethanol yield in SSCF. This is conceptually important for the design of novel SSCF processes aiming at high-ethanol titers. Substrate feeding prevents viscosity from becoming too high and thereby allows a higher total amount of WIS to be added in the process. The enzyme feeding, furthermore, enables keeping the glucose concentration low, which kinetically favors xylose uptake and results in a higher xylose conversion.</p

Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments

Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (Hg-II) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand

Controls on the composition and lability of dissolved organic matter in Siberia's Kolyma River basin

High-latitude northern rivers export globally significant quantities of dissolved organic carbon (DOC) to the Arctic Ocean. Climate change, and its associated impacts on hydrology and potential mobilization of ancient organic matter from permafrost, is likely to modify the flux, composition, and thus biogeochemical cycling and fate of exported DOC in the Arctic. This study examined DOC concentration and the composition of dissolved organic matter (DOM) across the hydrograph in Siberia's Kolyma River, with a particular focus on the spring freshet period when the majority of the annual DOC load is exported. The composition of DOM within the Kolyma basin was characterized using absorbance-derived measurements (absorbance coefficienta330, specific UV absorbance (SUVA254), and spectral slope ratio SR) and fluorescence spectroscopy (fluorescence index and excitation-emission matrices (EEMs)), including parallel factor analyses of EEMs. Increased surface runoff during the spring freshet led to DOM optical properties indicative of terrestrial soil inputs with high humic-like fluorescence, SUVA254, and low SRand fluorescence index (FI). Under-ice waters, in contrast, displayed opposing trends in optical properties representing less aromatic, lower molecular weight DOM. We demonstrate that substantial losses of DOC can occur via biological (∼30% over 28 days) and photochemical pathways (>29% over 14 days), particularly in samples collected during the spring freshet. The emerging view is therefore that of a more dynamic and labile carbon pool than previously thought, where DOM composition plays a fundamental role in controlling the fate and removal of DOC at a pan-Arctic scale