Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda ...and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1–3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd-type quinol oxidase or ba3-type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. Finally, these adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.
A fractured planar photonic crystal cavity is designed so that its resonant frequency can be mechanically tuned over a range of tens of nanometers while maintaining a quality factor in excess of ...100,000. Experimental data validates the tuning capability, in lower Q cavities.
Time Varying Functional Connectivity (TVFC) investigates how the interactions among brain regions vary over the course of an fMRI experiment. The transitions between different individual connectivity ...states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort as measured by pupil dilation. In this paper, we develop a multi-subject Bayesian framework for estimating dynamic functional networks as a function of time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach, where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states, borrowing strength over the entire time course of the experiment. The state-transition probabilities are assumed to vary over time and across subjects, as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. Our modeling approach further assumes sparsity in the network structures, via shrinkage priors. We achieve edge selection in the estimated graph structures, by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, leading us to assess the heterogeneity of the effects of changes in pupil dilation, previously linked to changes in norepinephrine-containing locus coeruleus, on the subjects' propensity to change connectivity states.
Nitrene transfer catalyzed by a d
0
zirconium(
iv
) complex with a redox-active ligand is reported. The redox-active ligand, bis(2-isopropylamido-4-methoxyphenyl)amide (NNN
cat
3−
), afforded ...zirconium(
iv
) complexes, NNN
cat
ZrClL
2
(
1a
, L = THF;
1b
, L = CN
t
Bu;
1c
, L = py), upon reaction with ZrCl
4
(THF)
2
. Complex
1a
was oxidized by one and two electrons using PhICl
2
, affording NNN
sq*
ZrCl
2
(THF) (
2
) and NNN
q
ZrCl
3
(
3
), respectively. Aryl azides reacted with
1a
to afford zirconium imide dimers, including the crystallographically characterized species {NNN
q
ZrCl(μ
2
-
p
-NC
6
H
4
t
Bu)}
2
(
4
). The formation of
4
is the result of the addition of an aryl nitrene to the zirconium(
iv
) metal center. When
1b
was reacted with organoazides, the dimer was not observed, but rather the nitrene group was transferred to the isonitrile to form a carbodiimide. In the presence of excess organoazide and isonitrile, catalytic carbodiimide formation occurred, showing that a redox-active ligand and a d
0
metal center can work in concert to effect nitrene group transfer reactivity.
A zirconium(
iv
), redox-active-ligand complex can catalyze nitrene transfer from organic azide to isonitrile to form a carbodiimide
Rho
A
plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo ...dramatic cytoskeletal changes and the
R
ho
A
protein level is up‐regulated. Transgenic mice were generated that express a dominant‐negative
R
ho
A
transgene in ameloblasts using amelogenin gene‐regulatory sequences. Transgenic and wild‐type (
WT
) molar tooth germs were incubated with sodium fluoride (
N
aF) or sodium chloride (
N
aCl) in organ culture. Filamentous actin (
F
‐actin) stained with phalloidin was elevated significantly in
WT
ameloblasts treated with
N
aF compared with
WT
ameloblasts treated with
N
aCl or with transgenic ameloblasts treated with
N
aF, thereby confirming a block in the
R
hoA/Rho‐associated protein kinase (
ROCK
) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between
WT
and transgenic incisors from mice provided with drinking water containing
N
aF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin,
E
‐cadherin, and
K
i67 compared with
WT
molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and
E
‐cadherin and cell proliferation are regulated by
R
ho
A
in other tissues. Together these findings reveal deficits in molar ameloblast function when
R
ho
A
activity is inhibited.
IntroductionAmong stented patients with atrial fibrillation (AF), double therapy with a novel oral anticoagulant (NOAC) plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular (CV) ...rehospitalizations compared to a vitamin K antagonist (VKA) based triple therapy regimen. However, it remains unknown whether a NOAC based double therapy is superior to a VKA based double therapy.HypothesisNOAC based double therapy will reduce the occurrence of all bleeding and CV rehospitalizations compared to VKA based double therapy among subjects in the PIONEER AF PCI trial.MethodsStented AF patient (n = 2,124) were randomized to three groupsrivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT) (Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Prior to randomization, subjects were stratified according to a pre-specified duration of DAPT (1, 6 or 12 months). Following the pre-specified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15mg plus low dose aspirin, and patients in Group 3 were switched to VKA plus low dose aspirin. The Wie, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and CV rehospitalizations among subjects on a NOAC versus VKA based double therapy.ResultsA total of 906 subjects were pre-specified to a DAPT duration of 1 or 6 months and received at least one dose of study drug. Twenty subjects (3.3%) assigned to NOAC + SAPT and 11 (17.2%) subjects assigned to VKA + SAPT experienced multiple reshopsitlizations. In total, 124 (20.3%) events occurred among subjects on NOAC + SAPT compared to 87 (29.6%) among subjects on VKA + SAPT (HR = 0.65, 95% CI0.45-0.93, p = 0.008) (Figure 1).ConclusionsAmong stented patients with AF, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and CV rehospitalization.
BackgroundBetrixaban reduced the occurrence of venous thrombosis, compared to enoxaparin, among patients hospitalized for acute medically illness. However, betrixaban’s role in reducing major adverse ...cardiovascular events among those with a history of ischemic events remains unknown.HypothesisFactor Xa inhibition with betrixaban in acutely ill hospitalized medical patients with a history of myocardial infarction (MI) or ischemic stroke is associated with a reduction in major adverse cardiovascular (CV) events compared to enoxaparin.MethodsThe APEX trial randomized 7,513 patients that were hospitalized for an acute medical illness to receive betrixaban for 35 to 42 days or enoxaparin for 6 to 14 days. Subjects were followed for up to 77 days. In the current analysis, the primary efficacy outcome was the composite of CV death, MI, or ischemic stroke among subjects with a history of MI or stroke. The primary safety outcome was the occurrence of major bleed within seven days of study drug discontinuation. Hazard ratios and 95% confidence intervals were calculated using a cox proportional hazard model. KM estimates were calculated and the log-rank p-value was reported.ResultsA total of 1597 subjects in the betrixaban arm and 1631 subjects in the enoxaparin arm had a history of stroke or myocardial infarction and received at least one dose of study drug. Fifty-six (3.6%) of subjects in the betrixaban arm and 83 (5.4%) subjects in the enoxaparin arm experienced an event. Betrixaban was associated with a significant reduction in CV death, MI, or ischemic stroke through 77 days compared to enoxaparin (HR = 0.69, 95% CI = 0.49-0.97, p = 0.031, ARR = 1.8%, NNT = 56) (Figure 1). Major bleeding was similar between the two treatment arms (p = 0.27).ConclusionAmong hospitalized acute medically ill patients with a history of MI or stroke, the administration of betrixaban for 35 to 42 days reduced the occurrence of CV death, MI, or ischemic stroke. These analyses build upon the primary APEX results to show that a single therapeutic strategy can yield positive outcomes among related arterial and venous vascular diseases such as DVT, PE, MI, and stroke.
France implemented a comprehensive smoke-free law in two phases: Phase 1 (February 2007) banned smoking in workplaces, shopping centres, airports, train stations, hospitals, and schools; Phase 2 ...(January 2008) banned smoking in hospitality venues (bars, restaurants, hotels, casinos, nightclubs). This paper evaluates France's smoke-free law based on the International Tobacco Control Policy Evaluation Project in France (the ITC France Project), which conducted a cohort survey of approximately 1,500 smokers and 500 non-smokers before the implementation of the laws (Wave 1) and two waves after the implementation (Waves 2 and 3). Results show that the smoke-free law led to a very significant and near-total elimination of observed smoking in key venues such as bars (from 94-97% to 4%) and restaurants (from 60-71% to 2-3%) at Wave 2, which was sustained four years later (6-8% in bars; 1-2% in restaurants). The reduction in self-reported smoking by smoking respondents was nearly identical to the effects shown in observed smoking. Observed smoking in workplaces declined significantly after the law (from 41-48% to 18-20%), which continued to decline at Wave 3 (to 14-15%). Support for the smoke-free laws increased significantly after their implementation and continued to increase at Wave 3 (p<.001 among smokers for bars and restaurants; p<.001 among smokers and p = .003 for non-smokers for workplaces). The findings demonstrate that smoke-free policies that are implemented in ways consistent with the Guidelines for Article 8 of the WHO Framework Convention on Tobacco Control (WHO FCTC) lead to substantial and sustained reductions in indoor smoking while also leading to high levels of support by the public. Moreover, contrary to arguments by opponents of smoke-free laws, smoking in the home did not increase after the law was implemented and prevalence of smoke-free homes among smokers increased from 23.2% before the law to 37.2% 5 years after the law.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundDecreased serum concentration of albumin, an acute-phase reactant with anticoagulant properties, may be associated with unfavorable prognosis in hospitalized patients.ObjectivesThe study ...aims to evaluate the relationship between albumin and venous thromboembolism (VTE) among hospitalized medical patients. Further, we assess the incremental prognostic impact of albumin to well-validated risk assessment models.MethodsThe APEX trial randomized 7513 acutely ill hospitalized patients to thromboprophylaxis with betrixaban or enoxaparin. The association of baseline albumin (as continuous or categorical variable) to VTE at 77 days was assessed by fitting logistic regression models. VTE risk refinement was evaluated by incorporation of albumin into the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score and Padua prediction score.ResultsBaseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints (median39 g/L; interquartile range35 to 42 g/L). A stepwise increase in the risk of VTE (P<0.0001), asymptomatic proximal deep vein thrombosis (aDVT) (P=0.0028), and VTE-related death (P<0.0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (<35 g/L) had a 2-fold greater risk for VTE compared with the top quartile (≥42 g/L) (OR=2.119 95% CI1.592-2.820). The risk of aDVT and VTE-related death was also higher in the <35 g/L group (OR=1.736 1.262-2.389 and OR=4.357 1.604-11.834, respectively). The odds for overall VTE and symptomatic VTE increased by 1.368 and 1.501 times per SD decrement of albumin (5.24 g/L). After adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (i.e., D-dimer and C-reactive protein), low albumin remained associated with an increased risk of VTE (OR=2.079 1.485-2.911). Albumin measurement significantly refined VTE risk discrimination and reclassification after inclusion in the IMPROVE score and Padua prediction score.ConclusionsThere was an inverse relationship between serum albumin and VTE risk through 77 days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.
BackgroundThe link between inflammation and a long-term risk for venous thromboembolism (VTE) is supported by population-based studies. It remains uncertain whether C-reactive protein (CRP), an ...inflammatory biomarker, would be associated with short-term VTE among acutely ill hospitalized patients despite provision of thromboprophylaxis.MethodsIn the APEX trial, 7513 acutely ill hospitalized patients were randomized to receive either extended-duration betrixaban or shorter-duration enoxaparin and followed for 77 days. CRP levels were measured at baseline from a central laboratory. The relationship between baseline CRP (as a continuous or categorical variable) and VTE was assessed by fitting a univariable and multivariable logistic regression model, with adjustment for thromboprophylaxis, index hospitalization event, D-dimer measurement, and other VTE risk factors (including previous history of VTE, thrombophilia, current lower-limb paralysis, cancer, intensive care unit stay, and age >60 years).ResultsBaseline CRP concentrations were obtained from 7320 subjects (median12.4 mg/L; interquartile range3.8 to 60.6 mg/L). The risk of VTE at 77 days appeared to increase with CRP elevation (P for trend <0.001; OR=1.25 95% CI1.10 to 1.43 per one-unit increase in log CRP). Additionally, patients at the upper CRP quartiles had a greater risk of VTE compared with the bottom quartile (≥60.6 vs. <3.8 mg/LOR=1.64 95% CI1.21 to 2.22; 12.4-60.6 vs. <3.8 mg/LOR=1.67 95% CI1.23 to 2.25). Patients with clinically significant inflammation (CRP >10 mg/L) were more likely to develop VTE (OR=1.33 95% CI1.08 to 1.64). After multivariable adjustment, elevated CRP remained associated with an increased risk of VTE (>10 vs. ≤10 mg/LOR=1.39 95% CI1.11 to 1.75).ConclusionsAmong acutely ill hospitalized patients, baseline CRP was independently associated with VTE risk through 77 days, suggesting a prognostic role for inflammation in VTE prediction.Figure. VTE risk stratified by CRP quartiles or clinical cutoff (>10 mg/L indicates clinically significant inflammation)
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