Background
The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory ...explanation.
Methods
An individual‐patient data meta‐analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm‐related mortality and reintervention.
Results
The analysis included 2783 patients, with 14 245 person‐years of follow‐up (median 5·5 years). Early (0–6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30‐day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm‐related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.
Conclusion
The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm‐related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR‐1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.
Survival comparable
Abstract Background Aortofemoral bypass(AFB), iliofemoral bypass(IFB), and aortoiliac endarterectomy(AIE) are the three most common techniques for anatomical open surgical revascularisation for ...patients with aorto-iliac occlusive disease(AIOD), but the optimal method of reconstruction is unknown. Aims To review and compare mortality, morbidity and short- and long-term patency rates for AFB, IFB and AIE in patients with AIOD reported in the English language literature Methods A MEDLINE(1970–2007) and Cochrane Library search for articles relating to AFB, IFB, AIE and AIOD was undertaken. Studies were included if: a) patency rates based on life-tables were available, and b) patient/study characteristics were reported. Results 29 studies(5738 patients) for AFB, 11 studies(778 patients) for IFB and 11 studies(1490 patients) for AIE were included. Operative mortality was 4.1% for AFB, 2.7% for IFB and 2.7% for AIE ( p < 0.0001). Systemic morbidity was 16.0% for AFB, 18.9% for IFB and 12.5% for AIE ( p < 0.05). Overall 5-year primary patency rates were 86.3%, 85.3% and 88.3% for AFB, IFB and AIE, respectively ( p = NS). Conclusion Aorto-iliac endarterectomy was associated with significantly lower peri-operative morbidity and mortality rates compared with bypass grafting. All three techniques were equally effective in terms of long-term patency.
Climate change is restructuring biodiversity on multiple scales and there is a pressing need to understand the downstream ecological and genomic consequences of this change. Recent advancements in ...the field of eco‐evolutionary genomics have sought to include evolutionary processes in forecasting species' responses to climate change (e.g., genomic offset), but to date, much of this work has focused on terrestrial species. Coastal and offshore species, and the fisheries they support, may be even more vulnerable to climate change than their terrestrial counterparts, warranting a critical appraisal of these approaches in marine systems. First, we synthesize knowledge about the genomic basis of adaptation in marine species, and then we discuss the few examples where genomic forecasting has been applied in marine systems. Next, we identify the key challenges in validating genomic offset estimates in marine species, and we advocate for the inclusion of historical sampling data and hindcasting in the validation phase. Lastly, we describe a workflow to guide marine managers in incorporating these predictions into the decision‐making process.
Predicting climate change impacts is of central importance in marine ecosystems that provide a major source of nutrition to global communities and this work must be based on a sound understanding of both ecological and genomic impacts. This opinion synthesizes knowledge about the genomic basis of adaptation in marine species, highlights the few examples where genomic forecasting has been applied in marine systems, identifies the key challenges in validating genomic offset estimates in marine species, and provides a workflow to guide marine managers in incorporating these predictions into the decision‐making process.
We present a detailed analysis of week-long simultaneous observations of the blazar Mrk 421 at 2-60 keV X-rays (RXTE) and TeV -rays (Whipple and HEGRA) in 2001. Accompanying optical monitoring was ...performed with the Mt. Hopkins 48 inch telescope. The unprecedented quality of this data set enables us to establish the existence of the correlation between the TeV and X-ray luminosities, and also to start unveiling some of its characteristics, in particular its energy dependence and time variability. The source shows strong variations in both X-ray and -ray bands, which are highly correlated. No evidence of an X-ray/-ray interband lag tau is found on the full week data set, with tau image 3 ks. A detailed analysis of the March 19 flare, however, reveals that data are not consistent with the peak of the outburst in the 2-4 keV X-ray and TeV band being simultaneous. We estimate a image ks TeV lag. The amplitudes of the X-ray and -ray variations are also highly correlated, and the TeV luminosity increases more than linearly with respect to the X-ray one. The high degree of correlation lends further support to the standard model in which a unique electron population produces the X-rays by synchrotron radiation and the -ray component by inverse Compton scattering. However, the finding that for the individual best observed flares the -ray flux scales approximately quadratically with respect to the X-ray flux poses a serious challenge to emission models for TeV blazars, as it requires rather special conditions and/or fine tuning of the temporal evolution of the physical parameters of the emission region. We briefly discuss the astrophysical consequences of these new findings in the context of the competing models for the jet emission in blazars.
There are challenges for researchers and clinicians to select the most appropriate physical activity tool, and a balance between precision and feasibility is needed. Currently it is unclear which ...physical activity tool should be used to assess physical activity in Bronchiectasis. The aim of this research is to compare assessment methods (pedometer and IPAQ) to our criterion method (ActiGraph) for the measurement of physical activity dimensions in Bronchiectasis (BE), and to assess their feasibility and acceptability.
Patients in this analysis were enrolled in a cross-sectional study. The ActiGraph and pedometer were worn for seven consecutive days and the IPAQ was completed for the same period. Statistical analyses were performed using SPSS 20 (IBM). Descriptive statistics were used; the percentage agreement between ActiGraph and the other measures were calculated using limits of agreement. Feedback about the feasibility of the activity monitors and the IPAQ was obtained.
There were 55 (22 male) data sets available. For step count there was no significant difference between the ActiGraph and Pedometer, however, total physical activity time (mins) as recorded by the ActiGraph was significantly higher than the pedometer (mean ± SD, 232 (75) vs. 63 (32)). Levels of agreement between the two devices was very good for step count (97% agreement); and variation in the levels of agreement were within accepted limits of ±2 standard deviations from the mean value. IPAQ reported more bouted- moderate - vigorous physical activity (MVPA) mean, SD; 167(170) vs 6(9) mins/day, and significantly less sedentary time than ActiGraph mean, SD; 362(115) vs 634(76) vmins/day. There were low levels of agreement between the two tools (57% sedentary behaviour; 0% MVPA
), with IPAQ under-reporting sedentary behaviour and over-reporting MVPA
compared to ActiGraph. The monitors were found to be feasible and acceptable by participants and researchers; while the IPAQ was accepta ble to use, most patients required assistance to complete it.
Accurate measurement of physical activity is feasible in BE and will be valuable for future trials of therapeutic interventions. ActiGraph or pedometer could be used to measure simple daily step counts, but ActiGraph was superior as it measured intensity of physical activity and was a more precise measure of time spent walking. The IPAQ does not appear to represent an accurate measure of physical activity in this population.
Clinical Trials Registration Number NCT01569009 : Physical Activity in Bronchiectasis.
Although Galactic cosmic rays (protons and nuclei) are widely believed to be mainly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly ...a century after their discovery. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size—more than 50 times the diameter of similar Galactic regions—uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density. The cosmic rays produced in the formation, life and death of massive stars in these regions are expected to produce diffuse -ray emission through interactions with interstellar gas and radiation. M82, the prototype small starburst galaxy, is predicted to be the brightest starburst galaxy in terms of -ray emission. Here we report the detection of >700-GeV -rays from M82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core, which is about 500 times the average Galactic density. This links cosmic-ray acceleration to star formation activity, and suggests that supernovae and massive-star winds are the dominant accelerators.
Salvage logging is common practice in the boreal forest of northeastern Alberta, Canada. Fire-killed aspen snags are harvested as soon as is feasible after fire, and in the case of the House River ...fire (which burned over 250,000
ha in May and June 2002), planning and harvesting began before the fire was extinguished and continued until summer 2003. The ecological consequences of salvage logging are poorly understood, and unknown for bryophytes. Frequency of bryophyte occurrence was sampled during the first (2003) and second (2004) growing seasons after fire, in both burned and salvage logged stands. Because many bryophytes are substrate-specific, and because burned wood and scorched soil are important post-fire substrates, bryophytes in these microhabitats were targeted. Post-fire specialists and ubiquitous species dominated the communities on both substrates in burned stands and included
Aulacomnium palustre,
Ceratodon purpureus,
Funaria hygrometrica,
Leptobryum pyriforme,
Marchantia polymorpha,
Pohlia nutans, and
Polytrichum juniperinum. Salvage logging had a greater negative affect on bryophytes on burned wood than those observed on scorched soil. On burned wood, species richness was lower and the community differed in salvage logged stands compared to burned stands; these observations were consistent over both years of study. On scorched soil, species richness was lower and community composition differed in salvage logged stands compared to burned stands in the first year after salvage logging, but these differences were overcome by the second year after salvage logging. To preserve bryophytes on a managed landbase, particularly those found on wood, management objectives should include provisions to protect bryophyte substrate.
Background Endovascular aneurysm repair (EVAR) is associated with an improved perioperative mortality compared to open surgical repair. This benefit may reflect reduced incidence of microvascular and ...macrovascular thrombotic complications after EVAR. Purpose The purpose of this study was to review and compare the effects of abdominal aortic aneurysm (AAA), open surgical repair, and EVAR on coagulation, fibrinolysis, and platelet activation. Methods A MEDLINE (1966-2010) and Cochrane library search for articles relating to the effects of AAA, open surgical repair, and EVAR on hemostasis was performed utilizing and cross-linking terms such as clotting, fibrinolysis, AAA, EVAR, and open surgical repair. Studies with a small cohort of patients (less than 7) or in which values of assessed biomarkers were not included were rejected. Results AAA is associated with increased thrombin generation, activity, and fibrin turnover as evidenced by increased plasma levels of thrombin-antithrombin III-complex (TAT), activated protein C-protein C inhibitor (APC-PCI), fibrin-monomer-fibrinogen (FM-F), F1+2, fibrinogen, and D-dimer. The extent of hemostatic derangement correlates with the volume of intraluminal thrombus. This procoagulant state is exaggerated in the immediate perioperative period after both open surgical repair and EVAR, but is attenuated at medium-term follow-up although not normalized. Conclusion The resultant prothrombotic diathesis after open surgical repair and EVAR may account for the high level of perioperative thrombotic complications.
Advances in the treatment of acute leukemia have resulted in significantly improved remission rates, although disease relapse poses a significant risk. By utilizing sensitive, non-invasive imaging ...guidance, detection of early leukemic infiltration and the extent of residual tumor burden after targeted therapy can be expedited, leading to more efficient treatment planning. We demonstrated marked survival benefit and therapeutic efficacy of a new-generation vascular disrupting agent, combretastatin-A1-diphosphate (OXi4503), using reporter gene-imaging technologies and mice systemically administered luc+ and GFP+ human leukemic cells (LCs). Before treatment, homing of double-transduced cells was serially monitored and whole-body cellular distributions were mapped using bioluminescence imaging (BLI). Imaging findings strongly correlated with quantitative GFP expression levels in solid organs/tissues, suggesting that the measured BLI signal provides a highly sensitive and reliable biomarker of tumor tissue burden in systemic leukemic models. Such optical technologies can thereby serve as robust non-invasive imaging tools for preclinical drug discovery and for rapidly screening promising therapeutic agents to establish potency, treatment efficacy and survival advantage. We further show that GFP+ HL-60 cells reside in close proximity to VE-cadherin- and CD31-expressing endothelial cells, suggesting that the perivascular niche may have a critical role in the maintenance and survival of LCs.
Background Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk of cognitive impairment, but their joint association is unknown. Study Design ...Prospective cohort study. Setting & Participants A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS (Reasons for Geographic and Racial Disparities in Stroke) Study. Predictors Albuminuria was assessed using urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. Outcomes Incident cognitive impairment was defined as score ≤4 on the 6-Item Screener at the last follow-up visit. Results During a mean follow-up of 3.8 ± 1.5 years, UACRs of 30-299 and ≥300 mg/g were associated independently with 31% and 57% higher risk of cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest for those with high eGFRs and attenuated at lower levels ( P = 0.04 for trend). Relative to eGFR ≥60 mL/min/1.73 m2 , eGFR <60 mL/min/1.73 m2 was not associated independently with cognitive impairment. However, after stratifying by UACR, eGFR <60 mL/min/1.73 m2 was associated with a 30% higher risk of cognitive impairment in participants with UACR <10 mg/g, but not higher UACRs ( P = 0.04 for trend). Limitations Single measures of albuminuria and eGFR, screening test of cognition. Conclusions When eGFR was preserved, albuminuria was associated independently with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR was associated independently with cognitive impairment. Albuminuria and low eGFR are complementary, but not additive, risk factors for incident cognitive impairment.
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