bluuebunny/crossref_metadata_2025_split huggingface dataset:
30-Year Mortality After Venous Thromboembolism
Authors: Søgaard Kirstine Kobberøe , Schmidt Morten , Pedersen Lars , Horváth–Puhó Erzsébet , Sørensen Henrik Toft 
Published: June 2014

Background—
Studies on long-term mortality after venous thromboembolism (VTE) are sparse.

Methods and Results—
Using Danish medical databases, we conducted a 30-year nationwide population-based cohort study of 128 223 patients with first-time VTE (1980–2011) and a comparison cohort of 640 760 people from the general population (without VTE) randomly matched by sex, year of birth, and calendar period. The mortality risks for patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (3.0% and 31% versus 0.4%). Using Cox regression, we assessed mortality rate ratios (MRRs) with 95% confidence intervals (CIs). The overall 30-year MRR was 1.55 (95% CI, 1.53–1.57) for DVT and 2.77 (95% CI, 2.74–2.81) for PE. The 30-day MRR was 5.38 (95% CI, 5.00–5.80) for DVT and 80.87 (95% CI, 76.02–86.02) for PE. Over time, the 30-day MRR was consistently 5- to 6-fold increased for DVT, whereas it improved for PE from 138 (95% CI, 125–153) in 1980 to 1989 to 36.08 (95% CI, 32.65–39.87) in 2000 to 2011. The 1- to 10-year and 11- to 30-year MRRs remained 25% to 40% increased after both DVT and PE but were 3- to 5-fold increased after DVT and 6- to 11-fold increased after PE when VTE was considered the immediate cause of death.

Conclusions—
Patients with VTE are at increased risk of dying, especially within the first year after diagnosis, but also during the entire 30 years of follow-up, with VTE as an important cause of death. Although 30-day mortality after DVT remained fairly constant over the last 3 decades, it improved markedly for PE.
Chronic Inflammatory Disorders and Risk of Type 2 Diabetes Mellitus, Coronary Heart Disease, and Stroke
Authors: Dregan Alex , Charlton Judith , Chowienczyk Phil , Gulliford Martin C. 
Published: June 2014

Background—
This study sought to evaluate whether risks of diabetes mellitus and cardiovascular disease are elevated across a range of organ-specific and multisystem chronic inflammatory disorders.

Methods and Results—
A matched cohort study was implemented in the UK Clinical Practice Research Datalink including participants with severe psoriasis (5648), mild psoriasis (85 232), bullous skin diseases (4284), ulcerative colitis (12 203), Crohn’s disease (7628), inflammatory arthritis (27 358), systemic autoimmune disorders (7472), and systemic vasculitis (6283) and in 373 851 matched controls. The main outcome measures were new diagnoses of type 2 diabetes mellitus, stroke, or coronary heart disease. The outcomes were evaluated for each condition in a multiple outcomes model, with adjustment for conventional cardiovascular risk factors. Estimates for different inflammatory conditions were pooled in a random-effects meta-analysis. There were 4695 new diagnoses of type 2 diabetes mellitus, 3266 of coronary heart disease, and 1715 of stroke. The hazard ratio for pooled multiple failure estimate was 1.20 (95% confidence interval [CI], 1.15–1.26). The highest relative hazards were observed in systemic autoimmune disorders (1.32; 95% CI, 1.16–1.50) and systemic vasculitis (1.29; 95% CI, 1.16–1.44). Hazards were increased in organ-specific disorders, including severe psoriasis (1.29; 95% CI, 1.12–1.47) and ulcerative colitis (1.26; 95% CI, 1.14–1.40). Participants in the highest tertile of C-reactive protein had greater risk of multiple outcomes (1.52; 95% CI, 1.37–1.68).

Conclusions—
The risk of cardiovascular diseases and type 2 diabetes mellitus is increased across a range of organ-specific and multisystem chronic inflammatory disorders with evidence that risk is associated with severity of inflammation. Clinical management of patients with chronic inflammatory disorders should seek to reduce cardiovascular risk.
Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study
Authors: Fretts Amanda M. , Mozaffarian Dariush , Siscovick David S. , Djousse Luc , Heckbert Susan R. , King Irena B. , McKnight Barbara , Sitlani Colleen , Sacks Frank M. , Song Xiaoling , Sotoodehnia Nona , Spiegelman Donna , Wallace Erin R. , Lemaitre Rozenn N. 
Published: June 2014

Background

Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (
AF
), but little is known about the associations of circulating saturated fatty acids with risk of
AF
.

Methods and Results

The study population included 2899 participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and
AF
in 1992. Cox regression was used to assess the association of all the long‐chain saturated fatty acids—palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)—with incident
AF
. During a median of 11.2 years of follow‐up, 707 cases of incident
AF
occurred. After adjustment for other
AF
risk factors, higher levels of circulating 16:0 were associated with a higher risk of
AF
(hazard ratio comparing highest and lowest quartiles: 1.48; 95%
CI
: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of
AF
. The hazard ratios (95%
CI
) for
AF
in the top and bottom quartiles were 0.76 (95%
CI
: 0.61, 0.95) for 18:0; 0.78 (95%
CI
: 0.63, 0.97) for 20:0; 0.62 (95%
CI
: 0.50, 0.78) for 22:0; and 0.68 (95%
CI
: 0.55, 0.85) for 24:0.

Conclusions

Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer‐chain saturated fatty acids with incident
AF
, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.
Heart Valve Prostheses in Pregnancy: Outcomes for Women and Their Infants
Authors: Lawley Claire M. , Algert Charles S. , Ford Jane B. , Nippita Tanya A. , Figtree Gemma A. , Roberts Christine L. 
Published: June 2014

Background
As the prognosis of women with prosthetic heart valves improves, and increasing number are contemplating and undertaking pregnancy. Accurate knowledge of perinatal outcomes is essential, assisting counseling and guiding care. The aims of this study were to assess outcomes in a contemporary population of women with heart valve prostheses undertaking pregnancy and to compare outcomes for women with mechanical and bioprosthetic prostheses.

Methods and Results

Longitudinally linked population health data sets containing birth and hospital admissions data were obtained for all women giving birth in New South Wales, Australia, 2000–2011. This included information identifying presence of maternal prosthetic heart valve. Cardiovascular and birth outcomes were evaluated. Among 1 144 156 pregnancies, 136 involved women with a heart valve prosthesis (1 per 10 000). No maternal mortality was seen among these women, although the relative risk for an adverse event was higher than the general population, including severe maternal morbidity (139 versus 14 per 1000 births, rate ratio [
RR
]=9.96, 95%
CI
6.32 to 15.7), major maternal cardiovascular event (44 versus 1 per 1000,
RR
34.6, 95%
CI
14.6 to 81.6), preterm birth (183 versus 66 per 1000,
RR
=2.77, 95%
CI
1.88 to 4.07), and small‐for‐gestational‐age infants (193 versus 95 per 1000,
RR
=2.03, 95%
CI
1.40 to 2.96). There was a trend toward increased maternal and perinatal morbidity in women with a mechanical valve compared with those with a bioprosthetic valve.

Conclusions
Pregnancies in women with a prosthetic heart valve demonstrate an increased risk of an adverse outcome, for both mothers and infants, compared with pregnancies in the absence of heart valve prostheses. In this contemporary population, the risk was lower than previously reported.
Racial Differences in the Association of Insulin Resistance With Stroke Risk
Authors: Howard George , Wagenknecht Lynne E. , Kernan Walter N. , Cushman Mary , Thacker Evan L. , Judd Suzanne E. , Howard Virginia J. , Kissela Brett M. 
Published: June 2014

Background and Purpose—
Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations.

Methods—
The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance.

Results—

There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR]
ln(IR)
=1.17; 95% confidence interval [CI], 1.00–1.38) but was largely attenuated by adjustment for stroke risk factors (HR
ln(IR)
=1.05; 95% CI, 0.88–1.26). There was no association in blacks (HR
ln(IR)
=1.01; 95% CI, 0.81–1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH (
P
=0.07), with a decrease in the risk of ICH in whites (HR
ln(IR)
=0.61; 95% CI, 0.35–1.04) but a nonsignificant increase in blacks (HR
ln(IR)
=1.20; 95% CI, 0.60–2.39).

Conclusions—
These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.
Blood Pressure Variability on Antihypertensive Therapy in Acute Intracerebral Hemorrhage
Authors: Tanaka Eijirou , Koga Masatoshi , Kobayashi Junpei , Kario Kazuomi , Kamiyama Kenji , Furui Eisuke , Shiokawa Yoshiaki , Hasegawa Yasuhiro , Okuda Satoshi , Todo Kenichi , Kimura Kazumi , Okada Yasushi , Okata Takuya , Arihiro Shoji , Sato Shoichiro , Yamagami Hiroshi , Nagatsuka Kazuyuki , Minematsu Kazuo , Toyoda Kazunori 
Published: June 2014

Background and Purpose—
The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort.

Methods—
Patients with hyperacute (<3 hours from onset) intracerebral hemorrhage with initial systolic BP (SBP) >180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4–6) at 3 months were assessed.

Results—
Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5–16.8) and 14.9 (11.7–17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5–11.2) and 13.1 (11.2–15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45–6.12 per quartile) and the successive variation of SBP (2.37; 1.32–4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04–1.97). Hematoma expansion was not associated with any BP variability.

Conclusions—
SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.
Postischemic Reperfusion Causes Smooth Muscle Calcium Sensitization and Vasoconstriction of Parenchymal Arterioles
Authors: Cipolla Marilyn J. , Chan Siu-Lung , Sweet Julie , Tavares Matthew J. , Gokina Natalia , Brayden Joseph E. 
Published: June 2014

Background and Purpose—
Parenchymal arterioles (PAs) are high-resistance vessels in the brain that connect pial vessels to the microcirculation. We previously showed that PAs have increased vasoconstriction after ischemia and reperfusion that could increase perfusion deficit. Here, we investigated underlying mechanisms by which early postischemic reperfusion causes increased vasoconstriction of PAs.

Methods—

Isolated and pressurized PAs from within the middle cerebral artery territory were studied in male Wistar rats that were either nonischemic control (n=34) or after exposure to transient middle cerebral artery occlusion (MCAO) by filament occlusion for 2 hours with 30 minutes of reperfusion (MCAO; n=38). The relationships among pressure-induced tone, smooth muscle calcium (using Fura 2), and membrane potential were determined. Sensitivity of the contractile apparatus to calcium was measured in permeabilized arterioles using
Staphylococcus aureus
α-toxin. Reactivity to inhibition of transient receptor potential melastanin receptor type 4 (9-phenanthrol), Rho kinase (Y27632), and protein kinase C (Gö6976) was also measured.

Results—

After MCAO, PAs had increased myogenic tone compared with controls (47±2% versus 35±2% at 40 mm Hg;
P
<0.01), without an increase in smooth muscle calcium (177±21 versus 201±16 nmol/L;
P
>0.05) or membrane depolarization (−38±4 versus −36±1 mV;
P
>0.05). In α-toxin–permeabilized vessels, MCAO caused increased sensitivity of the contractile apparatus to calcium. MCAO did not affect dilation to transient receptor potential melastanin receptor type 4 or protein kinase C inhibition but diminished dilation to Rho kinase inhibition.

Conclusions—
The increased vasoconstriction of PAs during early postischemic reperfusion seems to be due to calcium sensitization of smooth muscle and could contribute to infarct expansion and limit neuroprotective agents from reaching their target tissue.
The Importance of Wind and Buoyancy Forcing for the Boundary Density Variations and the Geostrophic Component of the AMOC at 26°N
Authors: Polo Irene , Robson Jon , Sutton Rowan , Balmaseda Magdalena Alonso 
Published: June 2014

AbstractIt is widely thought that changes in both the surface buoyancy fluxes and wind stress drive variability in the Atlantic meridional overturning circulation (AMOC), but that they drive variability on different time scales. For example, wind forcing dominates short-term variability through its effects on Ekman currents and coastal upwelling, whereas buoyancy forcing is important for longer time scales (multiannual and decadal). However, the role of the wind forcing on multiannual to decadal time scales is less clear. Here the authors present an analysis of simulations with the Nucleus for European Modelling of the Ocean (NEMO) ocean model with the aim of explaining the important drivers of the zonal density gradient at 26°N, which is directly related to the AMOC. In the experiments, only one of either the wind stress or the buoyancy forcing is allowed to vary in time, whereas the other remains at its seasonally varying climatology. On subannual time scales, variations in the density gradient, and in the AMOC minus Ekman, are driven largely by local wind-forced coastal upwelling at both the western and eastern boundaries. On decadal time scales, buoyancy forcing related to the North Atlantic Oscillation dominates variability in the AMOC. Interestingly, however, it is found that wind forcing also plays a role at longer time scales, primarily impacting the interannual variability through the excitation of Rossby waves in the central Atlantic, which propagate westward to interact with the western boundary, but also by modulating the decadal time-scale response to buoyancy forcing.
Evaluation of and Suggested Improvements to the WSM6 Microphysics in WRF-ARW Using Synthetic and Observed GOES-13 Imagery
Authors: Grasso Lewis , Lindsey Daniel T. , Sunny Lim Kyo-Sun , Clark Adam , Bikos Dan , Dembek Scott R. 
Published: June 2014

Abstract
Synthetic satellite imagery can be employed to evaluate simulated cloud fields. Past studies have revealed that the Weather Research and Forecasting (WRF) single-moment 6-class (WSM6) microphysics scheme in the Advanced Research WRF (WRF-ARW) produces less upper-level ice clouds within synthetic images compared to observations. Synthetic Geostationary Operational Environmental Satellite-13 (GOES-13) imagery at 10.7 μm of simulated cloud fields from the 4-km National Severe Storms Laboratory (NSSL) WRF-ARW is compared to observed GOES-13 imagery. Histograms suggest that too few points contain upper-level simulated ice clouds. In particular, side-by-side examples are shown of synthetic and observed anvils. Such images illustrate the lack of anvil cloud associated with convection produced by the 4-km NSSL WRF-ARW. A vertical profile of simulated hydrometeors suggests that too much cloud water mass may be converted into graupel mass, effectively reducing the main source of ice mass in a simulated anvil. Further, excessive accretion of ice by snow removes ice from an anvil by precipitation settling. Idealized sensitivity tests reveal that a 50% reduction of the accretion rate of ice by snow results in a significant increase in anvil ice of a simulated storm. Such results provide guidance as to which conversions could be reformulated, in a more physical manner, to increase simulated ice mass in the upper troposphere.
Access to cerebrospinal fluid in piglets via the cisterna magna: optimization and description of the technique
Authors: Romagnoli Noemi , Ventrella Domenico , Giunti Massimo , Dondi Francesco , Sorrentino Nicolina C , Fraldi Alessandro , Surace Enrico M , Bacci Maria L 
Published: June 2014

The collection of cerebrospinal fluid is necessary in order to determine its composition. It can then be used to diagnose various diseases. The aim of the study was to develop and optimize a technique for performing safe centesis for the collection of cerebrospinal fluid in piglets and its injection through the cisterna magna. The study was divided into three phases: (1) anatomical study of cadavers, (2) in vivo application of the technique and (3) observation of recovery time. The proposed technique resulted in a safe puncture of the cisterna magna. The authors identified and confirmed the correspondence of the crista occipitalis and the wings of the atlas with the external landmarks on the cadaver by means of direct radiological visualization. The punctures were performed successfully at the first attempt in 11 out of 12 anaesthetized piglets. The technique herein described provides a reproducible safe and easy route for approaching the cisterna magna for cerebrospinal fluid collection, drug administration and gene delivery.
An ab-initio analysis of the influence of knock-on atom induced damage on the peak tensile strength of 3C-SiC grain boundaries
Authors: Han You Sung , Tomar Vikas 
Published: June 2014

Abstract The effect of knock-on atom induced damage on the peak tensile strength of cubic silicon carbide (3C-SiC) is examined using an ab-initio simulation framework based on Car–Parrinello molecular dynamics (CPMD) method. The framework examines the effect of impact damage caused by a knock-on atom with velocities corresponding to four different kinetic energy levels (50 eV, 500 eV, 1 keV, and 2 keV) in three different SiC structure samples with different grain boundary (GB) configurations. Analyses show that peak tensile strength of the examined structures decreases by up to 37% in samples with GBs due to the impact damage caused by knock-on atom when compared with the case of single crystalline SiC under similar conditions. Analyses reveal new insights regarding the influence of bond strength change under knock-on atom induced impact damage on peak tensile strength of the examined structures. It is found that the peak tensile strength of the examined structures is a function of change in temperature, impact energy, and GB configuration. In order to extend the observed correlation of the peak tensile strength with atomic configurations to other structure types, a fractal dimension based approach is adopted to predict structure peak tensile strength as a function of knock-on atom impact energy, temperature, and GB configuration. Analyses show that the tensile strength of the examined SiC structures increases as a function of their fractal dimension increase. Fractal dimensions also change as a function of change in impact energy level and the corresponding damage in an inversely proportional manner. Based on the observed correlations, an empirical relation to predict structure peak tensile strength as a function of simulation parameters is developed. The developed relation is found to predict strength data of structures not included in the fitting with good accuracy.
A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy
Authors: Philip Brian , Kokalaki Evangelia , Mekkaoui Leila , Thomas Simon , Straathof Karin , Flutter Barry , Marin Virna , Marafioti Teresa , Chakraverty Ronjon , Linch David , Quezada Sergio A. , Peggs Karl S. , Pule Martin 
Published: June 2014

Key Points
Marker genes enable detection and selection of T cells, whereas suicide genes enable selective destruction of T cells in case of toxicity. RQR8 is a 136-amino-acid epitope-based marker/suicide gene that enables clinical selection, cell tracking, and deletion in case of toxicity.
HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies
Authors: Fernandez Christian A. , Smith Colton , Yang Wenjian , Daté Mihir , Bashford Donald , Larsen Eric , Bowman W. Paul , Liu Chengcheng , Ramsey Laura B. , Chang Tamara , Turner Victoria , Loh Mignon L. , Raetz Elizabeth A. , Winick Naomi J. , Hunger Stephen P. , Carroll William L. , Onengut-Gumuscu Suna , Chen Wei-Min , Concannon Patrick , Rich Stephen S. , Scheet Paul , Jeha Sima , Pui Ching-Hon , Evans William E. , Devidas Meenakshi , Relling Mary V. 
Published: June 2014

Key PointsHLA-DRB1*07:01 is associated with asparaginase hypersensitivity and anti-asparaginase antibodies. HLA-DRB1 alleles that confer high-affinity binding to asparaginase epitopes lead to a higher frequency of hypersensitivity.