bluuebunny/crossref_metadata_2025 huggingface dataset:
ARC15105 Is a Potent Antagonist of Von Willebrand Factor Mediated Platelet Activation and Adhesion
Authors: Siller-Matula Jolanta M. , Merhi Yahye , Tanguay Jean-François , Duerschmied Daniel , Wagner Denisa D. , McGinness Kathleen E. , Pendergrast P. Shannon , Chung Jou-Ku , Tian Xianbin , Schaub Robert G. , Jilma Bernd
Published: January 2012

Objective—

We investigated the stability, pharmacokinetic, and pharmacodynamic profile of the 2
nd
generation anti-von Willeband factor aptamer ARC15105.

Methods and Results—

Platelet plug formation was measured by collagen/adenosine diphosphate-induced closure time with the platelet function analyzer-100 and platelet aggregation by multiple electrode aggregometry. Platelet adhesion was measured on denuded porcine aortas and in a flow chamber. Aptamer stability was assessed by incubation in nuclease rich human, monkey, and rat serum for up to 72 hours. Pharmacokinetic and pharmacodynamic profiles were tested in cynomolgus monkeys after IV and SC administration. The median IC
100
and IC
50
to prolong collagen/adenosine diphosphate-induced closure timewere 27 nmol/L and 12 nmol/L, respectively. ARC15105 (1.3 μmol/L) completely inhibited ristocetin-induced platelet aggregation in whole blood (
P
<0.001), but also diminished collagen, ADP, arachidonic acid, and thrombin receptor activating peptide-induced platelet aggregation to some extent (
P
<0.05). ARC15105 (40 nmol/L) decreased platelet adhesion by >90% on denuded porcine aortas (
P
<0.001), which was comparable to the degree of inhibition obtained with abciximab. ARC15105 (100 nmol/L) also inhibited platelet adhesion to collagen under arterial shear in a flow chamber by >90% (
P
<0.001). The IV and SC terminal half-lives in cynomolgus monkeys were 67 and 65 hours, respectively, and the SC bioavailability was ≈98%. Allometric scaling estimates the human T
1/2
would be ≈217 hours. Pharmacodynamic analysis confirms that ARC15105 inhibits von Willeband factor activity >90% in blood samples taken 300 hours after a 20 mg/kg IV or SC dose in monkeys.

Conclusion—

The potency, pharmacokinetic profile, and SC bioavailability of ARC15105 support its clinical investigation for chronic inhibition of von Willeband factor -mediated platelet activation.
HNF4α Increases Liver-Specific Human ATP-Binding Cassette Transporter A1 Expression and Cholesterol Efflux to Apolipoprotein A-I in Response to Cholesterol Depletion
Authors: Ohoka Nobumichi , Okuhira Keiichiro , Cui Hongyan , Wu Weijia , Sato Ryuichiro , Naito Mikihiko , Nishimaki-Mogami Tomoko
Published: January 2012

Objective—

Hepatic ATP-binding cassette transporter A1 (ABCA1) plays the major role in maintaining plasma high-density lipoprotein levels by producing cholesterol-accepting nascent high-density lipoprotein, whereas peripheral ABCA1 is responsible for releasing cellular cholesterol. We previously reported that in rodents, cholesterol depletion reduces ABCA1 expression in peripheral but not hepatic cells by increasing a liver-specific
ABCA1
transcript via the sterol regulatory element-binding protein-2 system. However, the regulatory element is not conserved in humans. Here we investigated the mechanism of sterol-regulated human hepatic
ABCA1
gene expression.

Methods and Results—

ABCA1 mRNA
variant
type L3
is a novel and human-liver-specific transcript accounting for ≈25% of total
ABCA1
mRNA in the liver and is induced by cellular cholesterol depletion. Specific knockdown or forced expression revealed that
type L3
produces functional ABCA1 protein in cholesterol efflux. We identified a regulatory enhancer element for
L3
expression lying within intron 3 of the human
ABCA1
gene, to which hepatocyte nuclear factor (HNF) 4α binds in response to cholesterol depletion. HNF4α knockdown abolished induction of liver-specific
L3
and
L2b
transcripts (and consequently the liver-type response of ABCA1 expression to cellular cholesterol status) and diminished cholesterol efflux activity.

Conclusion—

These findings indicate that HNF4α regulates human hepatic ABCA1 expression in response to cholesterol depletion.
Flow Cytometric Identification and Functional Characterization of Immature and Mature Circulating Endothelial Cells
Authors: Mund Julie A. , Estes Myka L. , Yoder Mervin C. , Ingram David A. , Case Jamie
Published: January 2012

Objective—

We sought to identify and characterize 2 distinct populations of bona fide circulating endothelial cells, including the endothelial colony-forming cell (ECFC), by polychromatic flow cytometry (PFC), colony assays, immunomagnetic selection, and electron microscopy.

Methods and Results—

Mononuclear cells from human umbilical cord blood and peripheral blood were analyzed using our recently published PFC protocol. A population of cells containing both ECFCs and mature circulating endothelial cells was determined by varying expressions of CD34, CD31, and CD146 but not AC133 and CD45. After immunomagnetic separation, these cells failed to form hematopoietic colonies, yet clonogenic endothelial colonies with proliferative potential were obtained, thus verifying their identity as ECFCs. The frequency of ECFCs were increased in cord blood and were extremely rare in the peripheral blood of healthy adults. We also detected another mature endothelial cell population in the circulation that was apoptotic. Finally, when comparing this new protocol with a prior method, we determined that the present protocol identifies circulating endothelial cells, whereas the earlier protocol identified extracellular vesicles.

Conclusion—

Two populations of circulating endothelial cells, including the functionally characterized ECFC, are now identifiable in human cord blood and peripheral blood by PFC.
Nonesterified Fatty Acids and Risk of Sudden Cardiac Death in Older Adults
Authors: Djoussé Luc , Biggs Mary L. , Ix Joachim H. , Kizer Jorge R. , Lemaitre Rozenn N. , Sotoodehnia Nona , Zieman Susan J. , Mozaffarian Dariush , Tracy Russell P. , Mukamal Kenneth J. , Siscovick David S.
Published: January 2012

Background—

Although nonesterified fatty acids (NEFA) have been positively associated with coronary heart disease risk factors, limited and inconsistent data are available on the relation between NEFA and sudden cardiac death.

Methods and Results—

Using a prospective design, we studied 4657 older men and women (mean age, 75 years) from the Cardiovascular Health Study (1992–2006) to evaluate the association between plasma NEFA and the risk of sudden cardiac death in older adults. Plasma concentrations of NEFA were measured using established enzymatic methods, and sudden death was adjudicated using medical records, death certificates, proxy interview, and autopsy reports. We used Cox proportional hazard models to estimate multivariable-adjusted relative risks. During a median follow-up of 10.0 years, 221 new cases of sudden cardiac death occurred. In a multivariable model adjusting for age, sex, race, clinic site, alcohol intake, smoking, prevalent coronary heart disease and heart failure, and self-reported health status, relative risks (95% confidence interval) for sudden cardiac death were 1.0 (ref), 1.15 (0.81–1.64), 1.06 (0.72–1.55), and 0.91 (0.60–1.38) across consecutive quartiles of NEFA concentration. In secondary analyses restricted to the first 5 years of follow-up, we also did not observe a statistically significant association between plasma NEFA and sudden cardiac death.

Conclusions—

Our data do not provide evidence for an association between plasma NEFA measured late in life and the risk of sudden cardiac death in older adults.
Outcomes in Advanced Heart Failure Patients With Left Ventricular Assist Devices for Destination Therapy
Authors: Park Soon J. , Milano Carmelo A. , Tatooles Antone J. , Rogers Joseph G. , Adamson Robert M. , Steidley D. Eric , Ewald Gregory A. , Sundareswaran Kartik S. , Farrar David J. , Slaughter Mark S. ,   for the HeartMate II Clinical Investigators†
Published: January 2012

Background—

The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes.

Methods and Results—

Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year,
P
<0.001), sepsis (0.38 versus 0.27,
P
=0.025), device-related infections (0.47 versus 0.27,
P
<0.001), and hemorrhagic stroke (0.07 versus 0.03,
P
=0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year,
P
=0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group (
P
=0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke (
P
=0.01). Quality of life improvements were significant in both the groups (
P
<0.001).

Conclusions—

The benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00121485.
Necl-5/Poliovirus Receptor Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis
Authors: Kinugasa Mitsuo , Amano Hisayuki , Satomi-Kobayashi Seimi , Nakayama Kazuhiko , Miyata Muneaki , Kubo Yoshiki , Nagamatsu Yuichi , Kurogane Yusuke , Kureha Fumie , Yamana Shota , Hirata Ken-ichi , Miyoshi Jun , Takai Yoshimi , Rikitake Yoshiyuki
Published: January 2012

Rationale:

Vascular endothelial growth factor (VEGF), a major proangiogenic agent, exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2), the activity of which is regulated by direct interactions with other cell surface proteins, including integrin α
V
β
3
. However, how the interaction between VEGFR2 and integrin α
V
β
3
is regulated is not clear.

Objective:

To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin α
V
β
3
, regulates the interaction between VEGFR2 and integrin α
V
β
3
, and to clarify the role of Necl-5 in the VEGF-induced angiogenesis.

Methods and Results:

Necl-5-knockout mice displayed no obvious defect in vascular development; however, recovery of blood flow after hindlimb ischemia and the VEGF-induced neovascularization in implanted Matrigel plugs were impaired in Necl-5-knockout mice. To clarify the mechanism of the regulation of angiogenesis by Necl-5, we investigated the roles of Necl-5 in the VEGF-induced angiogenic responses in vitro. Knockdown of Necl-5 by siRNAs in human umbilical vein endothelial cells (HUVECs) inhibited the VEGF-induced capillary-like network formation on Matrigel, migration, and proliferation, and conversely, enhanced apoptosis. Coimmunoprecipitation assays showed the interaction of Necl-5 with VEGFR2, and knockdown of Necl-5 prevented the VEGF-induced interaction of integrin α
V
β
3
with VEGFR2. Knockdown of Necl-5 suppressed the VEGFR2-mediated activation of downstream proangiogenic and survival signals, including Rap1, Akt, and endothelial nitric oxide synthase.

Conclusions:

These results demonstrate the critical role of Necl-5 in angiogenesis and suggest that Necl-5 may regulate the VEGF-induced angiogenesis by controlling the interaction of VEGFR2 with integrin α
v
β
3
, and the VEGFR2-mediated Rap1-Akt signaling pathway.
High Levels of Costimulatory Receptors OX40 and 4-1BB Characterize CD4
+
CD28
null
T Cells in Patients With Acute Coronary Syndrome
Authors: Dumitriu Ingrid E. , Baruah Paramita , Finlayson Caroline J. , Loftus Ian M. , Antunes Ricardo F. , Lim Pitt , Bunce Nicholas , Carlos Kaski Juan
Published: January 2012

Rationale:

Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4
+
CD28
null
T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4
+
CD28
null
T cell function are unknown.

Objective:

Our aim was to investigate the expression and role of alternative costimulatory receptors in CD4
+
CD28
null
T cells in ACS.

Methods and Results:

Expression of alternative costimulatory receptors (inducible costimulator, OX40, 4–1BB, cytotoxic T lymphocyte associated antigen-4, programmed death-1) was quantified in CD4
+
CD28
null
T cells from circulation of ACS and stable angina patients. Strikingly, in ACS, levels of OX40 and 4-1BB were significantly higher in circulating CD4
+
CD28
null
T cells compared to classical CD4
+
CD28
+
T lymphocytes. This was not observed in stable angina patients. Furthermore, CD4
+
CD28
null
T cells constituted an important proportion of CD4
+
T lymphocytes in human atherosclerotic plaques and exhibited high levels of OX40 and 4-1BB. In addition, the ligands for OX40 and 4-1BB were present in plaques and also expressed on monocytes in circulation. Importantly, blockade of OX40 and 4-1BB reduced the ability of CD4
+
CD28
null
T cells to produce interferon-γ and tumor necrosis factor-α and release perforin.

Conclusions:

Costimulatory pathways are altered in CD4
+
CD28
null
T cells in ACS. We show that the inflammatory and cytotoxic function of CD4
+
CD28
null
T cells can be inhibited by blocking OX40 and 4-1BB costimulatory receptors. Modulation of costimulatory receptors may allow specific targeting of this cell subset and may improve the survival of ACS patients.
Thrombus Branching and Vessel Curvature Are Important Determinants of Middle Cerebral Artery Trunk Recanalization With Merci Thrombectomy Devices
Authors: Zhu Liangfu , Liebeskind David S. , Jahan Reza , Starkman Sidney , Salamon Noriko , Duckwiler Gary , Vinuela Fernando , Tateshima Satoshi , Gonzalez Nestor , Villablanca Pablo , Ali Latisha K. , Kim Doojin , Ovbiagele Bruce , Froehler Michael , Tenser Matthew , Saver Jeffrey L.
Published: January 2012

Background and Purpose—

Determinants of successful recanalization likely differ for Merci thrombectomy and intra-arterial pharmacological fibrinolysis interventions. Although the amount of thrombotic material to be digested is an important consideration for chemical lysis, mechanical debulking may be more greatly influenced by other target lesion characteristics.

Methods—

In consecutive patients with acute ischemic stroke treated with Merci thrombectomy for middle cerebral artery M1 occlusions, we analyzed the influence on recanalization success and clinical outcome of target thrombus size (length) and shape (curvature and branching) on pretreatment T2* gradient echo MRI.

Results—

Among 65 patients, pretreatment MRI showed susceptibility vessel signs in 45 (69%). Thrombus length averaged 13.03 mm (range, 5.56–34.91) and irregular shape (curvature or branching) was present in 17 of 45 (38%). Presence and length of susceptibility vessel signs did not predict recanalization or good clinical outcome. Substantial recanalization (Thrombolysis In Cerebral Infarction 2b or 3) and good clinical outcome (modified Rankin Scale score ≤2) were more frequent with regular than irregular susceptibility vessel signs shape (57% versus 18%,
P
=0.013; 39% versus 6%,
P
=0.017). On multiple regression analysis, the only independent predictor of substantial recanalization was irregular susceptibility vessel signs (OR, 0.16; 95% CI, 0.04–0.69;
P
=0.014); and leading predictors of good clinical outcome were baseline National Institutes of Health Stroke Scale (OR, 1.20; 95% CI, 1.03–1.40;
P
= 0.019) and irregular susceptibility vessel signs (OR, 9.36; 95% CI, 0.98–89.4;
P
=0.052).

Conclusions—

Extension of thrombus into middle cerebral artery division branches and curving shape of the middle cerebral artery stem, but not thrombus length, decrease technical and clinical success of Merci thrombectomy in M1 occlusions.
Organization of a United States County System for Comprehensive Acute Stroke Care
Authors: Cramer Steven C. , Stradling Dana , Brown David M. , Carrillo-Nunez Ignacio M. , Ciabarra Anthony , Cummings Michael , Dauben Richard , Lombardi David L. , Patel Nirav , Traynor Elizabeth N. , Waldman Stephen , Miller Ken , Stratton Samuel J.
Published: January 2012

Background and Purpose—

Organized systems of care have the potential to improve acute stroke care delivery. The current report describes the experience of implementing a county-wide system of spoke-and-hub stroke neurology receiving centers (SNRC) that incorporated several comprehensive stroke center recommendations.

Methods—

Observational study of patients with suspected stroke of <5 hours duration transported by emergency medical system personnel to an SNRC during the first year of this system.

Results—

A total of 1360 patients with suspected stroke were evaluated at 9 hub SNRC, of which 553 (40.7%) had a discharge diagnosis of ischemic stroke. Of these 553, intravenous tissue-type plasminogen activator was administered to 110 patients (19.9% of ischemic strokes). Care at the 6 neurointerventional-ready SNRC was a major focus in which 25.1% (99/395) of the patients with ischemic stroke received acute intravenous or intra-arterial reperfusion therapy, and in which provision of such therapies was less common with milder stroke, older age, and Hispanic origin. The door-to-needle time for intravenous tissue-type plasminogen activator met the <60-minute target in only 25% of patients and was 37% longer (
P
=0.0001) when SNRC were neurointerventional-ready.

Conclusions—

A stroke system that incorporates features of comprehensive stroke centers can be effectively implemented with substantial rates of acute reperfusion therapy administration. Experiences potentially useful to broader implementation of comprehensive stroke centers are considered.
Dual or Mono Antiplatelet Therapy for Patients With Acute Ischemic Stroke or Transient Ischemic Attack
Authors: Geeganage Chamila M. , Diener Hans-Christoph , Algra Ale , Chen Christopher , Topol Eric J. , Dengler Reinhard , Markus Hugh S. , Bath Matthew W. , Bath Philip M.W. ,   for the Acute Antiplatelet Stroke Trialists Collaboration
Published: January 2012

Background and Purpose—

Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack.

Methods—

Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI).

Results—

Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49–0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56–0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56–0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86–5.06).

Conclusions—

Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.
Impact of Emergency Department Transitions of Care on Thrombolytic Use in Acute Ischemic Stroke
Authors: Madej-Fermo Olga P. , Staff Ilene , Fortunato Gil , Abbott Lincoln , McCullough Louise D.
Published: January 2012

Background and Purpose—

In-hospital mortality is higher for certain medical conditions based on the time of presentation to the emergency department. The primary goal of this study was to determine whether patients with acute ischemic stroke who arrived to the emergency department during a nursing shift change had similar rates of thrombolytic use and functional outcomes compared with patients presenting during nonshift change hours.

Methods—

A retrospective review of patients with acute ischemic stroke presenting to the emergency department of a primary stroke center from 2005 through 2010. The time to notify the stroke team, perform a head CT scan, and to start intravenous or intra-arterial thrombolysis was assessed. Thrombolysis rates, mortality rate, discharge disposition, change in the National Institutes of Health Stroke Scale, and change in modified Barthel Index at 3 and 12 months were assessed.

Results—

Of 3133 patients with acute ischemic stroke, 917 met criteria for inclusion. Arrival during nursing shift change, weekends, and July through September had no impact on process times, thrombolysis rates, and functional outcomes. Arrival at night did result in longer time to intra-arterial but not to intravenous thrombolysis, higher mortality rate, and smaller gain in functional status as measured by the modified Barthel Index at 3 months. The degree of emergency department “busyness” also did not influence tissue-type plasminogen activator treatment times.

Conclusions—

Presentation during a nursing shift change, a time of transition of care, did not delay thrombolytic use in eligible patients with acute ischemic stroke. Presentation with acute ischemic stroke at night did result in delays of care for patients undergoing interventional therapies.
Intracerebral Hemorrhage in the Very Old
Authors: Stein Marco , Misselwitz Björn , Hamann Gerhard F. , Scharbrodt Wolfram , Schummer Dorothee I. , Oertel Matthias F.
Published: January 2012

Background and Purpose—

In most European societies and in the United States, the percentage of patients ≥80 years has been rising over the past century. The present study was conducted to observe this demographic change and its impact on patients with intracerebral hemorrhage (ICH).

Methods—

We reviewed patients' data with the diagnosis of ICH from January 2007 to December 2009. All data were collected out of a prospective stroke registry covering the entire state of Hesse, Germany. Incidence rates and absolute numbers of patients with ICH for 2009 to 2050 were calculated.

Results—

Of 3448 patients, 34% had an age ≥80 years. Hospital mortality was 35.9% for patients ≥80 years and 20.0% for patients <80 years. Unfavorable outcome (modified Rankin Scale score >2) was more often found in patients ≥80 years compared with patients <80 years (84.9% versus 74.8%). By the year 2050, the proportion of all patients with ICH ≥80 years will be 2.5-fold higher than in 2009. The total number of ICH cases will increase approximately 35.2% assuming that ICH probability stays the same. The number of patients who die in the hospital will increase approximately 60.2%. The total number of patients with severe disability due to ICH will increase approximately 36.8%.

Conclusions—

If current treatment strategies according to age remain unchanged, an increase of in-hospital mortality and a higher proportion of patients who need lifelong care after ICH can be expected in the coming decades.
Reduced Ipsilesional Cortical Volumes in Fetal Periventricular Venous Infarction
Authors: Li Damon , Hodge Jacquie , Wei Xing-Chang , Kirton Adam
Published: January 2012

Background and Purpose—

Perinatal stroke causes most term-born hemiplegic cerebral palsy. Many suffer additional sequelae. Periventricular venous infarction (PVI) is a common fetal stroke in which isolated subcortical injury may cause only motor deficits. However, cognitive, language, and behavioral deficits also occur. We hypothesized that ipsilesional cortical gray matter volumes are reduced in PVI.

Methods—

Children (12 months to 18 years) with MRI-confirmed PVI were identified through the Alberta Perinatal Stroke Project. We developed an MRI method to quantify sectional gray (GM) and white matter (WM) volumes from lesioned and unlesioned (control) hemispheres (OsiriX software). Differences in cortical GM and WM volumes were compared between hemispheres in preselected regions “above” the lesion (middle) and anterior and posterior to this. Outcomes dichotomized for “cortical dysfunction” (cognitive, behavioral, language) and motor deficit severity (Pediatric Stroke Outcome Measure) were compared with GM volumes.

Results—

Twenty-two children (81% boys; median age, 8 years) were included. Methods demonstrated high intrarater and inter-rater reliabilities (ρ=0.988, ρ=0.943) and minimal observer bias. Ipsilesional GM volume was significantly reduced in the middle (
P
=0.007) and posterior (
P
=0.03) regions. Middle ipsilesional WM volumes were reduced (
P
<0.001). The degree of GM reduction was not associated with cortical dysfunction or severity of motor deficit.

Conclusions—

Ipsilesional GM volume is diminished in PVI. Speculative mechanisms include retrograde neuronal degeneration and disrupted migration. Neuropsychological testing of larger samples is required to determine clinical significance.
The Climatology of Synoptic-Scale Ascent over Western North America: A Perspective on Storm Tracks
Authors: Lareau Neil P. , Horel John D.
Published: January 2012

The position and variability of storm tracks across western North America are examined during the October–April cool seasons spanning 1989–2010. The location and intensity of storms are represented by strong synoptic-scale ascent, which is diagnosed by the alternative balance omega equation applied to ECMWF Re-Analysis Interim data. This dynamically filtered method removes poorly resolved updrafts arising from subsynoptic-scale phenomena such as convection and mountain waves. The resulting vertical motions are illustrated for the case of a strong storm traversing the western United States.

Summary statistics of synoptic-scale ascent are compiled over months, seasons, and the entire 21-yr period. Locations exhibiting high mean values of ascent are deemed to represent storm tracks. The climatological-mean storm track exhibits a sinusoidal shape across the eastern Pacific and western North America. The composite evolution of strong storms moving along specific segments of the storm track show regional differences (e.g., storms poleward of 50°N tend to result from progressive low-amplitude troughs progressing through the mean planetary ridge, while storms over the western United States are initiated by digging troughs that temporarily suppress the mean ridge).

Seasonal shifts in the storm track are pronounced and exhibit coherent regional patterns. Interannual variations in synoptic-scale ascent indicate meridional shifts in position as well as changes in the degree of amplification within the dominant sinusoidal storm track. These changes in structure are related to the phase of ENSO: El Niño (La Niña) winters favor zonal (amplified) and southern (northern) storm tracks.
The HWRF Hurricane Ensemble Data Assimilation System (HEDAS) for High-Resolution Data: The Impact of Airborne Doppler Radar Observations in an OSSE
Authors: Aksoy Altuğ , Lorsolo Sylvie , Vukicevic Tomislava , Sellwood Kathryn J. , Aberson Sim D. , Zhang Fuqing
Published: January 2012

Within the National Oceanic and Atmospheric Administration, the Hurricane Research Division of the Atlantic Oceanographic and Meteorological Laboratory has developed the Hurricane Weather Research and Forecasting (HWRF) Ensemble Data Assimilation System (HEDAS) to assimilate hurricane inner-core observations for high-resolution vortex initialization. HEDAS is based on a serial implementation of the square root ensemble Kalman filter. HWRF is configured with a horizontal grid spacing of km on the outer/inner domains. In this preliminary study, airborne Doppler radar radial wind observations are simulated from a higher-resolution km version of the same model with other modifications that resulted in appreciable model error.

A 24-h nature run simulation of Hurricane Paloma was initialized at 1200 UTC 7 November 2008 and produced a realistic, category-2-strength hurricane vortex. The impact of assimilating Doppler wind observations is assessed in observation space as well as in model space. It is observed that while the assimilation of Doppler wind observations results in significant improvements in the overall vortex structure, a general bias in the average error statistics persists because of the underestimation of overall intensity. A general deficiency in ensemble spread is also evident. While covariance inflation/relaxation and observation thinning result in improved ensemble spread, these do not translate into improvements in overall error statistics. These results strongly suggest a need to include in the ensemble a representation of forecast error growth from other sources such as model error.
Should We Be Writing Essays Instead of Articles? A Psychotherapist’s Reflection on Montaigne’s Marvelous Invention
Authors: Starr Rachel
Published: January 2012

Contemporary psychology may be overlooking an important mode of inquiry by insisting that our primary mode of communication should take the form of scientific articles rather than that of literary essays. The essay was first practiced and then refined by Michel de Montaigne in the late Renaissance and constitutes a unique literary form that incorporates both Renaissance humanism and the then-emerging spirit of scientific discovery. The aim of the present essay is to explore the uses psychotherapists might make of Montaigne’s Essays, both as a fruitful model for writing about and for reflecting on the human condition. The essay was born at a time of great intellectual and spiritual upheaval and renewal. It is freewheeling, unorthodox, forever inventive, and at the same time learned, disciplined, and profoundly respectful of the past. The author looks to the humanist essay as developed by Montaigne as a useful literary and disciplinary device that can help in understanding the gap between purely theoretical or academic psychology and the actual practice of therapeutic psychology.
Peak-Experiences Among Americans in Midlife
Authors: Hoffman Edward , Kaneshiro Susan , Compton William C.
Published: January 2012

Though much attention, professionally and in popular American culture, has been accorded to midlife angst and turmoil, no published research has been conducted on peak-experiences during this major lifespan period. In this study, 153 people aged 40 to 65 years in the United States responded to a questionnaire asking them to describe a recent joyful experience and its subsequent impact on their outlook on life. They were also asked to rate it numerically on a 5-point Likert-type scale. Their qualitative reports were subsequently coded into 13 categories. Peaks involving interpersonal joy were reported significantly most frequently, more than all other categories combined. These were followed in frequency by those comprising respectively external achievement and personal growth. Small percentages involved religious peaks in either institutional or noninstitutional settings, recovery from illness/accident, nature, skill mastery, philosophical musing, developmental landmark, homecoming, nostalgia, and serenity. The implications for better understanding and optimizing midlife functioning are discussed, and future research avenues are highlighted.
The use of UKCP09 to produce weather files for building simulation
Authors: Mylona Anastasia
Published: January 2012

Traditionally, hourly weather years such as the test reference years (TRYs) and design summer years (DSYs) have been used for building energy and thermal performance analysis. Until recently, these weather datasets were based on observed measurements, but the need to adapt buildings to the impacts of likely future climate change has introduced a requirement to incorporate climate projections, such as the UK Climate Projections (UKCP09), into building performance analysis. Four research projects, funded by the EPSRC, examined the use of UKCP09 data, and the associated Weather Generator tool, in producing weather files appropriate for building simulation. A methodology called ‘morphing’, previously used to create the currently available to practitioners, UK Climate Impacts Programme (UKCIP02) based, CIBSE Future Weather Years, will also be discussed here as a potential alternative for the production of UKCP09-based weather files. This article reviews all above methodologies developed to produce weather files for building simulation, using the UKCP09 projections, and discusses their benefits and limitations as well as their ease of use by designers.

Practical application: This article aims to provide a comprehensive review of the various methodologies currently available for the production of future weather files for building thermal and energy performance simulation using the UKCP09 projections. This analysis aims to provide users with the benefits and limitations associated with each methodology and end product based on their accessibility, consistency with other currently used datasets, computational resources required and spatial availability.
Development of Sustain™
Authors: Guenter Peggi , Robinson Lawrence , DiMaria‐Ghalili Rose Ann , Lyman Beth , Steiger Ezra , Winkler Marion F.
Published: January 2012

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) developed a Web‐based registry for nutrition care launched in early 2011, initially focusing on the home parenteral nutrition (HPN) patient population. The purpose of Sustain is to collect information regarding the patients and populations who require HPN in the United States, measure outcomes associated with HPN, allow institutional benchmarking against the aggregate data, and publish the findings to improve the quality of care for patients receiving HPN. The registry is open to all sites (hospital and home based) who care for new or existing HPN patients. Preliminary data should be available in early 2012.
Composite Mandibulectomy
Authors: Sidell Douglas R. , Aghaloo Tara , Tetradis Sotirios , Lee Min , Bezouglaia Olga , DeConde Adam , St. John Maie A.
Published: January 2012

Objectives

Segmental mandibular defects can result after the treatment of various pathologic processes, including osteoradionecrosis, tumor resection, or fracture nonunion with sequestration. The variety of etiologies and the frequency of occurrence make the reconstruction of segmental mandibular defects a topic of significant interest. Despite these incentives, a well‐established small‐animal model of the segmental mandibulectomy, including composite resection, does not exist. The objective of this study is the creation of a reliable animal model that can be used to study the reconstruction of en bloc mandibular defects. Surgical techniques and an array of reconstructive options are described.

Study design

Description of an animal model.

Setting

Animal laboratory at a quaternary care university medical center.

Methods

We present an Animal Research Oversight Committee–approved prospective analysis of survival operations in the rat model. A detailed, stepwise description of surgical technique and relevant intraoperative anatomy is presented. Postoperative management, early pitfalls, surgical complications, and future applications are discussed.

Results

A total of 72 operations were performed by a single individual between July and October 2010. Two intraoperative and 9 postoperative complications were recognized. There were 6 orocutaneous fistulas, 2 abscesses, and 1 seroma. There were 4 fatalities, which were attributed to anesthetic complications (2, intraoperative), hematoma formation (1, postoperative), and foreign‐body aspiration (1, postoperative).

Conclusion

This novel animal model reliably replicates the en bloc segmental mandibular defects seen in our patient population and can be manipulated to achieve a wide variety of research objectives.
Individual working lives and collective action. An introduction to capability for work and capability for voice
Authors: Bonvin Jean-Michel
Published: January 2012

This article presents the capability approach as an alternative conceptual and normative framework to assess the impact and relevance of existing labour market regulations. In this perspective, what matters is not GDP growth or the overall employment rate, but the development of people’s real freedom to choose a job or an activity they have reason to value. The two key notions of ‘capability for work’ and ‘capability for voice’ are presented in detail, as well as the way to use them as a framework for scientific analysis and empirical research. The article strongly emphasizes the significant difference that the use of such tools makes when it comes to assessing the impact and relevance of collective regulations in the field of work.

Cet article présente l’approche par les capacités comme un cadre conceptuel et normatif alternatif pour évaluer l’impact et la pertinence des réglementations existantes du marché du travail. Dans cette perspective, ce qui importe, ce n’est pas la croissance du PIB ou le taux global d’emploi, mais le développement de la liberté effective des individus de choisir un emploi ou une activité qu’ils ont des raisons d’apprécier. Les deux notions essentielles de « capacité à exercer un travail » et de « capacité à faire entendre sa voix » sont présentées en détail, de même que la manière d’utiliser ces notions comme cadre d’analyse scientifique et de recherche empirique. L’article souligne fortement la différence considérable qu’entraîne l’utilisation de tels outils quand il s’agit d’évaluer l’impact et la pertinence des réglementations collectives dans le domaine du travail.

In diesem Beitrag wird der Ansatz der Verwirklichungschancen als alternativer konzeptueller und normativer Rahmen vorgeschlagen, um die Auswirkungen und die Relevanz der bestehenden Arbeitsmarktvorschriften zu bewerten. Unter diesem Gesichtspunkt ist nicht das BIP-Wachstum oder die Gesamtbeschäftigungsrate von Bedeutung, sondern die Entwicklung der realen Freiheit der Menschen, eine Arbeit oder Tätigkeit zu wählen, die sie wertschätzen. Die beiden zentralen Konzepte der “capability for work” (Verwirklichungschance im Arbeitsleben) und der “capability for voice” (Chance, für Arbeitnehmerbelange einzutreten) werden ausführlich beschrieben, und es wird erklärt, wie diese als Rahmen für die wissenschaftliche Analyse und empirische Forschungsarbeiten dienen. Der Beitrag unterstreicht den bedeutenden Vorteil, der sich aus der Verwendung derartiger Konzepte bei der Bewertung der Auswirkungen und der Relevanz kollektiver Regelungen im Arbeitsbereich ergibt.
Collective responsibility in the workplace from a capability perspective
Authors: Zimmermann Bénédicte
Published: January 2012

The article shows how a shift in perspective results from use of the capability approach in evaluating corporate activity: instead of a narrow focus on economic development, attention is paid also to the human development dimension. The author puts forward a conception of professional development resulting from the combined exercise of different capabilities, of which she discusses three essential dimensions, namely, freedom of choice, empowerment and collective responsibility. On the basis of a case study, she analyses the forms and founding principles of collective responsibility as related to individual capabilities. She describes how these factors impact on workplace participation procedures, and outlines the principles of justice that they entail. More broadly, she shows the tensions and new challenges to trade unionism and collective action thrown up by the need to combine individual and collective voice.

L’article montre le déplacement de perspective qu’induit le recours à l’approche par les capacités pour évaluer l’activité des entreprises: du strict développement économique à la prise en compte du développement humain. L’auteure avance une conception du développement professionnel comme résultant de l’exercice conjoint de différentes capacités dont elle discute trois dimensions essentielles: la liberté de choisir, le pouvoir d’agir et la responsabilité collective. A partir d’une étude de cas, elle analyse les formes et les fondements de la responsabilité collective mise en jeu par les capacités individuelles. Elle en relève les conséquences sur les procédures de participation dans l’entreprise et les principes de justice mis en œuvre. Plus largement, elle montre les tensions et les nouveaux défis qui en résultent pour le syndicalisme et l’action collective en vue de combiner « voice » individuelle et collective.

Der Beitrag beschreibt den Perspektivenwechsel, der sich aus der Verwendung des Ansatzes der Verwirklichungschancen für die Bewertung der Unternehmenstätigkeiten ergibt: Die Tätigkeit eines Unternehmens wird demnach nicht nur unter dem Gesichtspunkt der wirtschaftlichen Entwicklung, sondern auch der menschlichen Entwicklung bewertet. Die Autorin schlägt ein Konzept der beruflichen Entwicklung vor, das sich aus der gleichzeitigen Wahrnehmung verschiedener Verwirklichungschancen ergibt, und erörtert die drei wichtigsten Dimensionen dieser Chancen: Wahlfreiheit, Handlungsmöglichkeit und kollektive Verantwortung. Anhand einer Fallstudie werden die Formen und Grundlagen der kollektiven Verantwortung, die sich aus den individuellen Verwirklichungschancen ergibt, untersucht. Die Autorin erläutert die daraus resultierenden Folgen für die Partizipationsverfahren im Unternehmen sowie die Gerechtigkeitsprinzipien, die dabei angewandt werden. In einem weiteren Kontext ergeben sich daraus Spannungen und neue Herausforderungen für die Gewerkschaftsbewegung und kollektives Handeln, um individuelle und kollektive “Voice” miteinander zu verknüpfen.
Young Children Read and Improvise
Authors: Kenney Susan Hobson
Published: January 2012

This article discusses the creative, educational, and musical growth that comes from manipulating pieces of a music game. The importance of child-centered play is discussed, with a focus on children using icons to change the melodic and word order of a song. They then “read” the icons to sing their new creation. The music manipulatives are the creation of Barbara Andress.
Stigma Is Associated with Delays in Seeking Care among HIV-Infected People in India
Authors: Steward Wayne T. , Bharat Shalini , Ramakrishna Jayashree , Heylen Elsa , Ekstrand Maria L.
Published: January 2012

Background:

Stigma shapes the lives of people living with HIV and may affect their willingness to seek medical care. But treatment delays can compromise health and increase the risk of transmission to others.

Purpose:

To examine whether the 4 stigma manifestations— enacted (discrimination), vicarious (hearing stories of discrimination), felt normative (perceptions of stigma’s prevalence), and internalized (personal endorsement of stigma beliefs)—were linked with delays in seeking care among HIV-infected people in India.

Methods:

A cross-sectional survey was conducted with 961 HIV-positive men and women in Mumbai and Bengaluru.

Results:

Enacted and internalized stigmas were correlated with delays in seeking care after testing HIV positive. Depression symptoms mediated the associations of enacted and internalized stigmas with care-seeking delays, whereas efforts to avoiding disclosing HIV status mediated only the association between internalized stigma and care-seeking delays.

Conclusion:

It is vital to develop stigma reduction interventions to ensure timely receipt of care.
F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis
Authors: Gouw Samantha C. , van den Berg H. Marijke , Oldenburg Johannes , Astermark Jan , de Groot Philip G. , Margaglione Maurizio , Thompson Arthur R. , van Heerde Waander , Boekhorst Jorien , Miller Connie H. , le Cessie Saskia , van der Bom Johanna G.
Published: January 2012

This systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. A systematic literature search was performed to include cohort studies published in peer-reviewed journals with data on inhibitor incidences in the various F8 gene mutation types and a mutation detection rate of at least 80%. Pooled odds ratios (ORs) of inhibitor development for different types of F8 gene mutations were calculated with intron 22 inversion as the reference. Data were included from 30 studies on 5383 patients, including 1029 inhibitor patients. The inhibitor risk in large deletions and nonsense mutations was higher than in intron 22 inversions (pooled OR = 3.6, 95% confidence interval [95% CI], 2.3-5.7 and OR = 1.4, 95% CI, 1.1-1.8, respectively), the risk in intron 1 inversions and splice-site mutations was equal (pooled OR = 0.9; 95% CI, 0.6-1.5 and OR = 1.0; 95% CI, 0.6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar.
Plasma biomarkers of lower gastrointestinal and liver acute GVHD
Authors: Harris Andrew C. , Ferrara James L. M. , Braun Thomas M. , Holler Ernst , Teshima Takanori , Levine John E. , Choi Sung W. , Landfried Karin , Akashi Koichi , Lugt Mark Vander , Couriel Daniel R. , Reddy Pavan , Paczesny Sophie
Published: January 2012

The lower gastrointestinal tract (LGI) and liver are the GVHD target organs most associated with treatment failure and nonrelapse mortality. We recently identified regenerating islet-derived 3-α (REG3α) as a plasma biomarker of LGI GVHD. We compared REG3α with 2 previously reported GI and liver GVHD diagnostic biomarkers, hepatocyte growth factor (HGF) and cytokeratin fragment 18, in 954 hematopoietic cell transplantation patients. All 3 biomarkers were significantly elevated in LGI GVHD compared with non-GVHD diarrhea; REG3α discerned LGI GVHD from non-GVHD diarrhea better than HGF and cytokeratin fragment 18. Although all 3 biomarkers predicted nonresponse to therapy at day 28 in LGI GVHD patients, only REG3α and HGF concentrations predicted 1-year nonrelapse mortality (P = .01 and P = .02, respectively). Liver GVHD without GI involvement at GVHD onset and non-GVHD liver complications were uncommon; all 3 biomarkers were elevated in liver GVHD, but did not distinguish GVHD from other causes of hyperbilirubinemia.