Continental-scale assessment of genetic diversity and population structure in quaking aspen (Populus tremuloides)

Aim: Quaking aspen (Populus tremuloides) has the largest natural distribution of any tree native to North America. The primary objectives of this study were to characterize range-wide genetic diversity and genetic structuring in quaking aspen, and to assess the influence of glacial history and rear-edge dynamics. Location: North America. Methods: Using a sample set representing the full longitudinal and latitudinal extent of the species’ distribution, we examined geographical patterns of genetic diversity and structuring using 8 nuclear microsatellite loci in 794 individuals from 30 sampling sites. Results: Two major genetic clusters were identified across the range: a southwestern cluster and a northern cluster. The south-western cluster, which included two subclusters, was bounded approximately by the Continental Divide to the east and the southern extent of the ice sheet at the Last Glacial Maximum to the north. Subclusters were not detected in the northern cluster, despite its continent-wide distribution. Genetic distance was significantly correlated with geographical distance in the south-western but not the northern cluster, and allelic richness was significantly lower in south-western sampling sites compared with northern sampling sites. Population structuring was low overall, but elevated in the south-western cluster. Main conclusions: Aspen populations in the south-western portion of the range are consistent with expectations for a historically stable edge, with low within-population diversity, significant geographical population structuring, and little evidence of northward expansion. Structuring within the southwestern cluster may result from distinct gene pools separated during the Pleistocene and reunited following glacial retreat, similar to patterns found in other forest tree species in the western USA. In aspen, populations in the southwestern portion of the species range are thought to be at particularly high risk of mortality with climate change. Our findings suggest that these same populations may be disproportionately valuable in terms of both evolutionary potential and conservation value

Development of a risk adjustment mortality model using the American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR) experience: 1998–2000

AbstractObjectivesWe sought to develop and evaluate a risk adjustment model for in-hospital mortality following percutaneous coronary intervention (PCI) procedures using data from a large, multi-center registry.BackgroundThe 1998–2000 American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR) dataset was used to overcome limitations of prior risk-adjustment analyses.MethodsData on 100,253 PCI procedures collected at the ACC–NCDR between January 1, 1998, and September 30, 2000, were analyzed. A training set/test set approach was used. Separate models were developed for presentation with and without acute myocardial infarction (MI) within 24 h.ResultsFactors associated with increased risk of PCI mortality (with odds ratios in parentheses) included cardiogenic shock (8.49), increasing age (2.61 to 11.25), salvage (13.38) urgent (1.78) or emergent PCI (5.75), pre-procedure intra-aortic balloon pump insertion (1.68), decreasing left ventricular ejection fraction (0.87 to 3.93), presentation with acute MI (1.31), diabetes (1.41), renal failure (3.04), chronic lung disease (1.33); treatment approaches including thrombolytic therapy (1.39) and non-stent devices (1.64); and lesion characteristics including left main (2.04), proximal left anterior descending disease (1.97) and Society for Cardiac Angiography and Interventions lesion classification (1.64 to 2.11). Overall, excellent discrimination was achieved (C-index = 0.89) and application of the model to high-risk patient groups demonstrated C-indexes exceeding 0.80. Patient factors were more predictive in the MI model, while lesion and procedural factors were more predictive in the analysis of non-MI patients.ConclusionsA risk adjustment model for in-hospital mortality after PCI was successfully developed using a contemporary multi-center registry. This model is an important tool for valid comparison of in-hospital mortality after PCI

A contemporary overview of percutaneous coronary interventions The American College of Cardiology–National Cardiovascular Data Registry (ACC–NCDR)

AbstractObjectivesThe American College of Cardiology (ACC) established the National Cardiovascular Data Registry (ACC–NCDR) to provide a uniform and comprehensive database for analysis of cardiovascular procedures across the country. The initial focus has been the high-volume, high-profile procedures of diagnostic cardiac catheterization and percutaneous coronary intervention (PCI).BackgroundSeveral large-scale multicenter efforts have evaluated diagnostic catheterization and PCI, but these have been limited by lack of standard definitions and relatively nonuniform data collection and reporting methods.MethodsBoth clinical and procedural data, and adverse events occurring up to hospital discharge, were collected and reported according to uniform guidelines using a standard set of 143 data elements. Datasets were transmitted quarterly to a central facility for quality-control screening, storage and analysis. This report is based on PCI data collected from January 1, 1998, through September 30, 2000.ResultsA total of 139 hospitals submitted data on 146,907 PCI procedures. Of these, 32% (46,615 procedures) were excluded because data did not pass quality-control screening. The remaining 100,292 procedures (68%) were included in the analysis set. Average age was 64 ± 12 years; 34% were women, 26% had diabetes mellitus, 29% had histories of prior myocardial infarction (MI), 32% had prior PCI and 19% had prior coronary bypass surgery. In 10% the indication for PCI was acute MI ≤6 h from onset, while in 52% it was class II to IV or unstable angina. Only 5% of procedures did not have a class I indication by ACC criteria, but this varied by hospital from a low of 0 to a high of 38%. A coronary stent was placed in 77% of procedures, but this varied by hospital from a low of 0 to a high of 97%. The frequencies of in-hospital Q-wave MI, coronary artery bypass graft surgery and death were 0.4%, 1.9% and 1.4%, respectively. Mortality varied by hospital from a low of 0 to a high of 4.2%.ConclusionsThis report presents the first data collected and analyzed by the ACC–NCDR. It portrays a contemporary overview of coronary interventional practices and outcomes, using uniform data collection and reporting standards. These data reconfirm overall acceptable results that are consistent with other reported data, but also confirm large variations between individual institutions

Tree-ring analysis of the fungal disease Swiss needle cast in western Oregon coastal forests

Swiss needle cast (SNC), an important fungal disease of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), has increased in severity throughout its natural and introduced range over the last half century. The role of climate change and forest management practices in the increase is unclear. We analyzed tree-ring chronologies from six late-successional Douglas-fir stands in the western Oregon Coast Range using time-series intervention analysis (TSIA) to address how climate relates to the impact of SNC on tree growth. Tree-ring chronologies of western hemlock (Tsuga heterophylla (Raf.) Sarg.), a species not susceptible to the fungus Phaeocryptopus gaeumannii (Rhode) Petrak, were used as a climate proxy in the TSIA. We found that growth reductions associated with SNC dated back to the 1590s, the earliest record in our dendritic data. Growth reductions were synchronous across the six sites, indicating that the disease severity was largely influenced by climatic conditions. SNC impact peaked in 1984-1986 at all six study sites, followed by unprecedented disease impacts of 100% in 1996 and 2004 at one site, while decreasing to previous levels at the other five sites. Our SNC index of impact significantly correlated with winter and summer temperatures and summer precipitation. Winter conditions were more strongly associated with disease impact at wetter, cooler sites, whereas summer conditions were more important at less humid, warmer sites. With climate change, SNC impacts are likely to increase in coastal areas where June-July precipitation is much higher than the P. gaeumannii-limiting threshold of similar to 110 mm, and decrease where summer precipitation is at or below the threshold. Warmer winters will increase disease severity at higher elevation, north along the coast from northern Oregon to British Columbia, and at inland sites where current winter temperatures limit fungal growth.Keywords: History, Intervention analysis, Douglas-fir plantations, Phaeocryptopus gaeumannii, British Columbia, New Zealand, Climate change, Pacific northwest, Time series, Severit

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Islands of ice: Influence of free-drifting Antarctic icebergs on pelagic marine ecosystems

Regional warming around West Antarctica, including the Antarctic Peninsula, is related to the retreat of glaciers that has resulted in significant ice mass loss in recent decades. We examined freedrifting icebergs in the Atlantic sector of the Southern Ocean in December 2005, aboard ARSV Laurence M. Gould, and in June 2008 and March/April 2009, aboard RVIB Nathaniel B. Palmer. Prior to these studies, little information was available about the effects of icebergs on the pelagic realm.Facultad de Ciencias Naturales y Muse

Reduction in downstream test utilization following introduction of coronary computed tomography in a cardiology practice

To compare utilization of non-invasive ischemic testing, invasive coronary angiography (ICA), and percutaneous coronary intervention (PCI) procedures before and after introduction of 64-slice multi-detector row coronary computed tomographic angiography (CCTA) in a large urban primary and consultative cardiology practice. We utilized a review of electronic medical records (NotesMD®) and the electronic practice management system (Megawest®) encompassing a 4-year period from 2004 to 2007 to determine the number of exercise treadmill (TME), supine bicycle exercise echocardiography (SBE), single photon emission computed tomography (SPECT) myocardial perfusion stress imaging (MPI), coronary calcium score (CCS), CCTA, ICA, and PCI procedures performed annually. Test utilization in the 2 years prior to and 2 years following availability of CCTA were compared. Over the 4-year period reviewed, the annual utilization of ICA decreased 45% (2,083 procedures in 2004 vs. 1,150 procedures in 2007, P < 0.01) and the percentage of ICA cases requiring PCI increased (19% in 2004 vs. 28% in 2007, P < 0.001). SPECT MPI decreased 19% (3,223 in 2004 vs. 2,614 in 2007 P < 0.02) and exercise stress treadmill testing decreased 49% (471 in 2004 vs. 241 in 2007 P < 0.02). Over the same period, there were no significant changes in measures of practice volume (office and hospital) or the annual incidence of PCI (405 cases in 2004 vs. 326 cases in 2007) but a higher percentage of patients with significant disease undergoing PCI 19% in 2004 vs. 29% in 2007 P < 0.01. Implementation of CCTA resulted in a significant decrease in ICA and a corresponding significant increase in the percentage of ICA cases requiring PCI, indicating that CCTA resulted in more accurate referral for ICA. The reduction in unnecessary ICA is associated with avoidance of potential morbidity and mortality associated with invasive diagnostic testing, reduction of downstream SPECT MPI and TME as well as substantial savings in health care dollars

Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond ( 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honorari

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes