To date, the therapeutic benefit of revascularization vs. medical therapy for stable individuals undergoing invasive coronary angiography (ICA) based upon coronary computed tomographic angiography ...(CCTA) findings has not been examined.
We examined 15 223 patients without known coronary artery disease (CAD) undergoing CCTA from eight sites and six countries who were followed for median 2.1 years (interquartile range 1.4-3.3 years) for an endpoint of all-cause mortality. Obstructive CAD by CCTA was defined as a ≥50% luminal diameter stenosis in a major coronary artery. Patients were categorized as having high-risk CAD vs. non-high-risk CAD, with the former including patients with at least obstructive two-vessel CAD with proximal left anterior descending artery involvement, three-vessel CAD, and left main CAD. Death occurred in 185 (1.2%) patients. Patients were categorized into two treatment groups: revascularization (n = 1103; 2.2% mortality) and medical therapy (n = 14 120, 1.1% mortality). To account for non-randomized referral to revascularization, we created a propensity score developed by logistic regression to identify variables that influenced the decision to refer to revascularization. Within this model (C index 0.92, χ2 = 1248, P < 0.0001), obstructive CAD was the most influential factor for referral, followed by an interaction of obstructive CAD with pre-test likelihood of CAD (P = 0.0344). Within CCTA CAD groups, rates of revascularization increased from 3.8% for non-high-risk CAD to 51.2% high-risk CAD. In multivariable models, when compared with medical therapy, revascularization was associated with a survival advantage for patients with high-risk CAD hazards ratio (HR) 0.38, 95% confidence interval 0.18-0.83, with no difference in survival for patients with non-high-risk CAD (HR 3.24, 95% CI 0.76-13.89) (P-value for interaction = 0.03).
In an intermediate-term follow-up, coronary revascularization is associated with a survival benefit in patients with high-risk CAD by CCTA, with no apparent benefit of revascularization in patients with lesser forms of CAD.
Across their range jaguars Panthera onca are important conservation icons for several reasons: their important role in ecosystems as top carnivores, their cultural and economic value, and their ...potential conflicts with livestock. However, jaguars have historically been difficult to monitor. This paper outlines the first application of a systematic camera trapping methodology for abundance estimation of jaguars. The methodology was initially developed to estimate tiger abundance in India. We used a grid of camera traps deployed for 2 months, identified individual animals from their pelage patterns, and estimated population abundance using capture-recapture statistical models. We applied this methodology in a total of five study sites in the Mayan rainforest of Belize, the Chaco dry forest of Bolivia, and the Amazonian rainforest of Bolivia. Densities were 2.4–8.8 adult individuals per 100 km2, based on 7–11 observed animals, 16–37 combined ‘captures’ and ‘recaptures’, 486–2,280 trap nights, and sample areas of 107–458 km2. The sampling technique will be used to continue long-term monitoring of jaguar populations at the same sites, to compare with further sites, and to develop population models. This method is currently the only systematic population survey technique for jaguars, and has the potential to be applied to other species with individually recognizable markings.
Sampling animal populations with camera traps has become increasingly popular over the past two decades, particularly for species that are cryptic, elusive, exist at low densities or range over large ...areas. The results have been widely used to estimate population size and density. We analyzed data from 13 camera trap surveys conducted at five sites across the Kaa‐Iya landscape, Bolivian Chaco, for jaguar, puma, ocelot and lowland tapir. We compared two spatially explicit capture–recapture (SCR) software packages: secr, a likelihood‐based approach, and SPACECAP, a Bayesian approach, both of which are implemented within the R environment and can be used to estimate animal density from photographic records of individual animals that simultaneously employ spatial information about the capture location relative to the sample location. As a non‐spatial analysis, we used the program CAPTURE 2 to estimate abundance from the capture–recapture records of individuals identified through camera trap photos combined with an ad hoc estimation of the effective survey area to estimate density. SCR methods estimated jaguar population densities from 0.31 to 1.82 individuals per 100 km2 across the Kaa‐Iya sites; puma from 0.36 to 7.99; ocelot from 1.67 to 51.7; and tapir from 7.38 to 42.9. Density estimates using either secr or SPACECAP were generally lower than the estimates generated using the non‐spatial method for all surveys and species; and density estimates using SPACECAP were generally lower than that using secr. We recommend using either secr or SPACECAP because the spatially explicit methods are not biased by an informal estimation of an effective survey area. Although SPACECAP and secr are less sensitive than non‐spatial methods to the size of the grid used for sampling, we recommend grid sizes several times larger than the average home range (known or estimated) of the target species.
Recent work in combustion and atmospheric chemistry has revealed cases in which diastereomers must be distinguished to accurately model a reacting flow. This paper presents an open-source framework ...for introducing such stereoisomer resolution into a kinetic mechanism. We detail our definitions and algorithms for labeling and enumerating the stereoisomers of a molecule and then generalize our system to describe the transition state (TS) of a reaction. This allows for the stereospecific enumeration of reactants and products while accounting for “fleeting” stereochemistry that is unique to the TS. We also present the AutoMech Chemical Identifier (AMChI), an InChI-like string identifier that accounts for stereocenters omitted by InChI. This identifier is extended to describe the TSs of reactions, providing a universal lookup key for specific reaction channels. The final piece of our methodology is an analytic formula to remove redundancy from a stereoresolved mechanism when its enantiomers exist as a racemic mixture, making it as compact as possible while fully accounting for the differences between diastereomers. In applying our methodology to two subsets of the NUIGMech1.1 mechanism, we find that our approach reduces the extra species added for large-fuel oxidation from 2231 (133%, full expansion) to 694 (41%, nonredundant expansion). We also find that for pyrolysis more than a quarter of the species in the expanded mechanism cannot be properly described by an InChI string, requiring an AMChI string to communicate their identity. Finally, we find that roughly one-quarter of the large-fuel oxidation reactions and one-third of the pyrolysis reactions include fleeting TS stereochemistry, which may have relevant effects on their kinetics.
Highlights • Machine learning tool for replanning and adaptive RT. • Multicenter investigation of predictive methods in Head and Neck cancer. • Support decision making tool to support physician ...activities. • Re-planning approach and benefit based on information acquirable by IGRT.
Background. Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. Methods. In a cross-sectional study of haemodialysis ...patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation BMI, albumin and C reactive protein (CRP) by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. Results. Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3±3.8 vs 24.4±4.7 kg/m2, P<0.001; and 3.8±0.6 vs 4.1±0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37±15 to 25±10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R2 = 0.22). Conclusions. Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.
The 2010-2011 Canterbury earthquake sequence provides a rare opportunity to study the performance of modern structures designed under well-enforced, evolving seismic code provisions and subjected to ...severe ground shaking. In particular, New Zealand makes widespread use of precast concrete seismic systems, including those that are designed to respond identically to cast-in-place concrete structures (emulative systems) and, in more recent years, those that take advantage of the unique jointed properties of precast construction. New Zealand building construction also makes extensive use of precast elements for gravity systems, floor systems, stairs, and cladding. Although not always classified as part of the primary seismic force-resisting system, these "secondary" elements must undergo the compatible displacements imposed in the earthquake. Damage evaluations for several of these structures subjected to strong shaking provide the ability to examine the differences in seismic performance for systems of distinct design intent and standards, including the performance of secondary elements.
Natural disturbances including wildfire, insects and disease are a growing threat to the remaining late successional forests in the Pacific Northwest, USA. These forests are a cornerstone of the ...region's ecological diversity and provide essential habitat to a number of rare terrestrial and aquatic species including the endangered northern spotted owl (
Strix occidentalis caurina). Wildfires in particular have reduced the amount of late successional forests over the past decade, prompting land managers to expand investments in forest management in an attempt to slow losses and mitigate wildfire risk. Much of the emphasis is focused specifically on late successional reserves established under the Northwest Forest Plan to provide habitat for spotted owls. In this paper, we demonstrate a probabilistic risk analysis system for quantifying wildfire threats to spotted owl habitat and comparing the efficacy of fuel treatment scenarios. We used wildfire simulation methods to calculate spatially explicit probabilities of habitat loss for fuel treatment scenarios on a 70,245
ha study area in Central Oregon, USA. We simulated 1000 wildfires with randomly located ignitions and weather conditions that replicated a recent large fire within the study area. A flame length threshold for each spotted owl habitat stand was determined using the forest vegetation simulator and used to predict the proportion of fires that resulted in habitat loss. Wildfire modeling revealed a strong spatial pattern in burn probability created by natural fuel breaks (lakes and lava flows). We observed a non-linear decrease in the probability of habitat loss with increasing treatment area. Fuels treatments on a relatively minor percentage of the forested landscape (20%) resulted in a 44% decrease in the probability of spotted owl habitat loss averaged over all habitat stands. The modeling system advances the application of quantitative and probabilistic risk assessment for habitat and species conservation planning.
ABSTRACT
Alström Syndrome (ALMS), a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multisystem involvement including early cone‐rod retinal dystrophy and ...blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis, and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of ALMS. Mutational analysis in a world‐wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with ALMS, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all ALMS1 mutations identified to date.
Alström Syndrome is a rare (<1/1,000,000) genetic disorder affecting multiple organ systems. In this report, we expand the spectrum of mutations of ALMS1 by mutational analysis in a world‐wide cohort of 204 families. We identified 109 novel mutations. We also provide an overview of the 240 known ALMS1 mutations identified to date and highlighting the allelic heterogeneity of this disorder. Additionally, we analyzed next generation sequencing data from 275 patients for rare or frequent Single Nucleotide Variants (SNVs).
•We proposed an automated tractography approach for individualized TAI detection.•We tested the feasibility of automated tractography in patients with acute severe TBI.•We investigated associations ...with behavioral measures of consciousness.•The TRACULA pipeline successfully reconstructed 93% of the tracts across patients.•The pipeline accurately discriminated between patients and controls (AUC: 0.91)
New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 ± 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 ± 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.1 ± 7.9) and accurately discriminated between patients and controls (AUC: 0.91). The number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients, respectively), consistent with prior histopathological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe TBI.
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