bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors
Authors: Manzoor Ashley A. , Lindner Lars H. , Landon Chelsea D. , Park Ji-Young , Simnick Andrew J. , Dreher Matthew R. , Das Shiva , Hanna Gabi , Park Won , Chilkoti Ashutosh , Koning Gerben A. , ten Hagen Timo L.M. , Needham David , Dewhirst Mark W.
Published: September 2012

Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566–75. ©2012 AACR.
Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients
Authors: Brown Janet E. , Cook Richard J. , Lipton Allan , Coleman Robert E.
Published: September 2012

Purpose: Survival is highly variable in women with bone metastases from breast cancer and prognostic factors are needed. We analyzed data from a phase III trial comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer and bone metastases to identify variables prognostic for overall survival.

Experimental Design: Patients who received ZOL (n = 435) with bone marker assessments and complete baseline data were included. Relative risks (RR) of death over 24 months were assessed using a stratified Cox regression analysis. A reduced model was generated using stepwise backward elimination until only significant (P < 0.05) variables remained.

Results: Only 5 of 19 variables analyzed remained significantly prognostic for survival in the reduced multivariate model. These included age more than 50 years (RR 1.78–2.53, P ≤ 0.01 for each decade >50 versus ≤50); Functional Assessment of Cancer Therapy-General (FACT-G) score less than 65 units (P < 0.05 vs. ≥75 units); impaired (PS ≥ 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG) performance status (RR 1.74, P < 0.01); prior versus no prior chemotherapy (RR 1.97; P < 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase ≥ upper limit of normal (ULN) but < 2 × ULN correlated with a two-fold increased risk of death, and LDH > 2 × ULN correlated with a six-fold increased risk of death versus LDH < ULN (P < 0.0001 for both). Baseline bone marker levels were not significantly correlated with survival after adjustment for other significant covariates.

Conclusions: This retrospective analysis shows that LDH levels correlate strongly with survival in patients with bone metastases from breast cancer and confirms the relevance of previously described prognostic factors. Clin Cancer Res; 18(22); 6348–55. ©2012 AACR.
TLE1 Is an Anoikis Regulator and Is Downregulated by Bit1 in Breast Cancer Cells
Authors: Brunquell Chris , Biliran Hector , Jennings Scott , Ireland Shubha Kale , Chen Renwei , Ruoslahti Erkki
Published: September 2012

TLE1 is a Groucho-related transcriptional repressor protein that exerts survival and antiapoptotic function in several cellular systems and has been implicated in the pathogenesis of cancer. In the present study, we found that TLE1 is a regulator of anoikis in normal mammary epithelial and breast carcinoma cells. The induction of apoptosis following loss of cell attachment to the extracellular matrix (anoikis) in untransformed mammary epithelial MCF10A cells was associated with significant downregulation of TLE1 expression. Forced expression of exogenous TLE1 in these cells promoted resistance to anoikis. In breast cancer cells, TLE1 expression was significantly upregulated following detachment from the extracellular matrix. Genetic manipulation of TLE1 expression via overexpression and downregulation approaches indicated that TLE1 promotes the anoikis resistance and anchorage-independent growth of breast carcinoma cells. Mechanistically, we show that TLE1 inhibits the Bit1 anoikis pathway by reducing the formation of the proapoptotic Bit1-AES complex in part through sequestration of AES in the nucleus. The mitochondrial release of Bit1 during anoikis as well as exogenous expression of the cytoplasmic localized Bit1 or its cell death domain induced cytoplasmic translocation and degradation of nuclear TLE1 protein. These findings indicate a novel role for TLE1 in the maintenance of anoikis resistance in breast cancer cells. This conclusion is supported by an immunohistochemical analysis of a breast cancer tissue array illustrating that TLE1 is selectively upregulated in invasive breast tumors relative to noninvasive ductal carcinoma in situ and normal mammary epithelial tissues. Mol Cancer Res; 10(11); 1482–95. ©2012 AACR.
Phylogenetic and Physicochemical Analyses Enhance the Classification of Rare Nonsynonymous Single Nucleotide Variants in Type 1 and 2 Long-QT Syndrome
Authors: Giudicessi John R. , Kapplinger Jamie D. , Tester David J. , Alders Marielle , Salisbury Benjamin A. , Wilde Arthur A.M. , Ackerman Michael J.
Published: September 2012

Background—

Hundreds of nonsynonymous single nucleotide variants (nsSNVs) have been identified in the 2 most common long-QT syndrome-susceptibility genes (
KCNQ1
and
KCNH2
). Unfortunately, an ≈3% background rate of rare
KCNQ1
and
KCNH2
nsSNVs amongst healthy individuals complicates the ability to distinguish rare pathogenic mutations from similarly rare yet presumably innocuous variants.

Methods and Results—

In this study, 4 tools [(1) conservation across species, (2) Grantham values, (3) sorting intolerant from tolerant, and (4) polymorphism phenotyping] were used to predict pathogenic or benign status for nsSNVs identified across 388 clinically definite long-QT syndrome cases and 1344 ostensibly healthy controls. From these data, estimated predictive values were determined for each tool independently, in concert with previously published protein topology–derived estimated predictive values, and synergistically when ≥3 tools were in agreement. Overall, all 4 tools displayed a statistically significant ability to distinguish between case-derived and control-derived nsSNVs in
KCNQ1
, whereas each tool, except Grantham values, displayed a similar ability to differentiate
KCNH2
nsSNVs. Collectively, when at least 3 of the 4 tools agreed on the pathogenic status of C-terminal nsSNVs located outside the KCNH2/Kv11.1 cyclic nucleotide−binding domain, the topology-specific estimated predictive value improved from 56% to 91%.

Conclusions—

Although in silico prediction tools should not be used to predict independently the pathogenicity of a novel, rare nSNV, our results support the potential clinical use of the synergistic utility of these tools to enhance the classification of nsSNVs, particularly for Kv11.1’s difficult to interpret C-terminal region.
Guideline Adherence After ST-Segment Elevation Versus Non-ST Segment Elevation Myocardial Infarction
Authors: Somma Keith A. , Bhatt Deepak L. , Fonarow Gregg C. , Cannon Christopher P. , Cox Margueritte , Laskey Warren , Peacock W. Frank , Hernandez Adrian F. , Peterson Eric D. , Schwamm Lee , Saxon Leslie A.
Published: September 2012

Background—

Clinical guidelines recommend similar medical therapy for patients with ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation MI (NSTEMI).

Methods and Results—

Using the Get with the Guidelines–Coronary Artery Disease registry (GWTG–CAD), we analyzed data including 72 352 patients (48 966, NSTEMI; 23 386, STEMI) from 237 US sites between May 1, 2006 and March 21, 2010. Performance and quality measures were compared between NSTEMI and STEMI patients. NSTEMI patients were older and had a higher rate of medical comorbidities compared with STEMI patients, including prior coronary artery disease (38.5% versus 24.7%;
P
<0.0001), heart failure (17.5% versus 6.2%;
P
<0.0001), hypertension (70.8% versus 59.1%;
P
<0.0001) and diabetes mellitus (34.9 versus 23.3%;
P
<0.0001). Adjusting for confounding variables, STEMI patients were more likely to receive aspirin within 24 hours 98.5% versus 97.1% (adjusted odds ratio [AOR], 1.63; 95% confidence interval [CI], 1.32–2.02), be discharged on aspirin 98.5% versus 97.3% (AOR, 1.33; 95% CI, 1.19–1.49), β-blockers 98.2% versus 96.9% (AOR, 1.48; 95% CI, 1.35–1.63), or lipid-lowering medication for low-density lipoprotein level >100 mg/dL 96.8% versus 91.0% (AOR, 1.85; 95% CI, 1.61–2.13). STEMI patients were also more likely to receive β-blockers within 24 hours of hospital arrival 93.9% versus 90.8% (AOR, 1.57; 95% CI, 1.37–1.79) and the following discharge medications: angiotensin-converting enzyme inhibitors or angiotensin receptor blocking agents 85.3% versus 77.4% (AOR, 1.62; 95% CI, 1.51–1.75), clopidogrel 85.6% versus 67.0% (AOR, 2.42; 95% CI, 2.23–2.61) or lipid-lowering medications 94.8% versus 88.0% (AOR, 1.71; 95% CI, 1.56–1.86).

Conclusions—

Among hospitals participating in GWTG–CAD, adherence with guideline-based medical therapy was high for patients with both STEMI and NSTEMI. Yet, there is still room for further improvement, particularly in the care of NSTEMI patients.
Left Ventricular Ejection Fraction Assessment Among Patients With Acute Myocardial Infarction and Its Association With Hospital Quality of Care and Evidence-Based Therapy Use
Authors: Miller Amy Leigh , Dib Chadi , Li Li , Chen Anita Y. , Amsterdam Ezra , Funk Marjorie , Saucedo Jorge F. , Wang Tracy Y.
Published: September 2012

Background—

The left ventricular ejection fraction (LVEF) has prognostic and therapeutic utility after acute myocardial infarction (AMI). Although LVEF assessment is a key performance measure among AMI patients, contemporary rates of in-hospital assessment and its association with therapy use have not been well characterized.

Methods and Results—

We examined rates of in-hospital LVEF assessment among 77 982 non–ST-elevation myocardial infarction patients and 50 863 ST-elevation myocardial infarction patients in Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines between January 2007 and September 2009, after excluding patients who died in-hospital or who were transferred to another acute care facility, discharged to end-of-life care, or had missing LVEF assessment status. LVEF assessment increased significantly over time, with higher rates among ST-elevation myocardial infarction than non–ST-elevation myocardial infarction patients (95.1% versus 91.6%;
P
<0.001). Excluding patients with prior heart failure did not alter these observations. Significant interhospital variability in LVEF assessment rates was observed. Compared with patients with in-hospital LVEF assessment, patients who did not have LVEF assessed were older and more likely to have clinical comorbidities. In multivariable modeling, lower overall hospital quality of AMI care was also associated with lower likelihood of LVEF assessment (odds ratio for failure to assess LVEF, 1.09; 95% confidence interval, 1.05–1.13 per 10% decrease in defect-free care). Patients with in-hospital LVEF assessment were more likely to be discharged on evidence-based secondary prevention medication therapies compared with paients without LVEF assessment.

Conclusions—

The assessment of LVEF among patients with AMI has improved significantly over time, yet significant interhospital variability exists. Patients who did not have in-hospital LVEF assessment were less likely to receive evidence-based medications at discharge. These patients represent targets for future quality improvement efforts.
Impact of Door-to-Activation Time on Door-to-Balloon Time in Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarctions
Authors: McCabe James M. , Armstrong Ehrin J. , Hoffmayer Kurt S. , Bhave Prashant D. , MacGregor John S. , Hsue Priscilla , Stein John C. , Kinlay Scott , Ganz Peter
Published: September 2012

Background—

Little is known about the components of door-to-balloon time among patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. We assessed the role of time from hospital arrival to ST-segment elevation myocardial infarction diagnosis (door-to-activation time) on door-to-balloon time in contemporary practice and evaluated factors that influence door-to-activation times.

Methods and Results—

Registry data on 347 consecutive patients diagnosed with a ST-segment elevation myocardial infarction in the emergency department over 30 months at 2 urban primary percutaneous coronary intervention centers were analyzed. The primary study end point was the time from hospital arrival to catheterization laboratory activation by the emergency department physician, and we assessed factors associated with this period. Door-to-balloon time and its other components were secondary study end points. The median door-to-activation time was 19 minutes (interquartile range, 9–54). Variation in door-to-activation times explained 93% of the variation in door-to-balloon times and demonstrated the strongest correlation with door-to-balloon times (
r
=0.97). Achieving a door-to-activation time of ≤20 minutes resulted in an 89% chance of achieving a door-to-balloon time of ≤90 minutes compared with only 28% for patients with a door-to-activation time >20 minutes. Factors significantly associated with door-to-activation time include the following: prehospital ECG use (61% shorter, 95% confidence interval, −50 to −72%;
P
<0.001) and computed tomography scan use in the emergency department (245% longer, 95% confidence interval, +50 to +399%;
P
=0.001).

Conclusions—

The interval from hospital arrival to ST-segment elevation myocardial infarction diagnosis and catheterization laboratory activation (door-to-activation time) is a strong driver of overall door-to-balloon times. Achieving a door-to-activation time ≤20 minutes was key to achieving a door-to-balloon time ≤90 minutes. Delays in door-to-activation time are not associated with delays in other aspects of the primary percutaneous coronary intervention process.
National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011
Authors: Kirley Kate , Qato Dima M. , Kornfield Rachel , Stafford Randall S. , Alexander G. Caleb
Published: September 2012

Background—

Little is known regarding the adoption of direct thrombin inhibitors in clinical practice. We examine trends in oral anticoagulation for the prevention of thromboembolism in the United States.

Methods and Results—

We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to quantify patterns of oral anticoagulant use among all subjects and stratified by clinical indication. We quantified oral anticoagulant expenditures using the IMS Health National Prescription Audit. Between 2007 and 2011, warfarin treatment visits declined from ≈2.1 million (M) quarterly visits to ≈1.6M visits. Dabigatran use increased from 0.062M quarterly visits (2010Q4) to 0.363M visits (2011Q4), reflecting its increasing share of oral anticoagulant visits from 3.1% to 18.9%. In contrast to warfarin, the majority of dabigatran visits have been for atrial fibrillation, though this proportion decreased from 92% (2010Q4) to 63% (2011Q4), with concomitant increases in dabigatran’s off-label use. Among atrial fibrillation visits, warfarin use decreased from 55.8% visits (2010Q4) to 44.4% (2011Q4), whereas dabigatran use increased from 4.0% to 16.9%. Of atrial fibrillation visits, the fraction not treated with any oral anticoagulants has remained unchanged at ≈40%. Expenditures related to dabigatran increased rapidly from $16M in 2010Q4 to $166M in 2011Q4, exceeding expenditures on warfarin ($144M) in 2011Q4.

Conclusions—

Dabigatran has been rapidly adopted into ambulatory practice in the United States, primarily for treatment of atrial fibrillation, but increasingly for off-label indications. We did not find evidence that it has increased overall atrial fibrillation treatment rates.
Achievement of Cardiometabolic Goals in Aware Hypertensive Patients in Spain
Authors: Banegas José R. , Graciani Auxiliadora , de la Cruz-Troca Juan J. , León-Muñoz Luz M. , Guallar-Castillón Pilar , Coca Antonio , Ruilope Luis M. , Rodríguez-Artalejo Fernando
Published: September 2012

Despite the importance of achieving cardiometabolic goals beyond blood pressure, in the health of hypertensives, no comprehensive assessment of these characteristics has been performed in whole countries. We studied in 2008–2010 a total of 11 957 individuals representative of the Spanish population aged ≥18 years. Information on cardiometabolic characteristics was collected at the participants’ homes, through structured questionnaires, physical examination, and fasting blood samples. A total of 3983 individuals (33.3%) had hypertension (≥140/90 mm Hg or current antihypertensive drug treatment), 59.4% were aware of their condition, 78.8% treated among those aware, and 48.5% controlled among those aware and treated (22.7% of all hypertensives). Of the aware hypertensives, 13.8% had a body mass index <25 kg/m
2
, 38.6% consumed <2.4 g/d of sodium, 19.3% were diabetic with 61% attaining goal hemoglobin A1c <6.5%, whereas 42.3% had hypercholesterolemia, with 38.1% reaching goal low-density lipoprotein <115 mg/dL. Only 30.7% of overweight patients received a prescription of specific method for weight loss, 17.4% of daily smokers were offered a smoking cessation strategy, and 15.8% of older patients were given a flu shot. Aware and unaware hypertensives showed a similar frequency of some lifestyle, such as adequate physical activity. In conclusion, in a European country with a well-developed, free-access healthcare system, achievement of many cardiometabolic goals among hypertensives is poor. Moreover, a serious deficiency in hypertension awareness and in the effectiveness of some lifestyle interventions among aware hypertensives is present. Greater effort is needed in the management of coexisting risk factors and on lifestyle medical advice to improve the cardiometabolic health of hypertensives
Association of Genetic Variation in the Mitochondrial Genome With Blood Pressure and Metabolic Traits
Authors: Liu Chunyu , Yang Qiong , Hwang Shih-Jen , Sun Fengzhu , Johnson Andrew D. , Shirihai Orian S. , Vasan Ramachandran S. , Levy Daniel , Schwartz Faina
Published: September 2012

Elevated blood pressure (BP) is a major risk factor for cardiovascular disease. Several studies have noted a consistent maternal effect on BP; consequently, mitochondrial DNA variation has become an additional target of investigation of the missing BP heritability. Analyses of common mitochondrial DNA polymorphisms, however, have not found evidence of association with hypertension. To explore associations of uncommon (frequency >5%) mitochon drial DNA variants with BP, we identified uncommon/rare variants through sequencing the entire mitochondrial genome in 32 unrelated individuals with extreme-high BP in the Framingham Heart Study and genotyped 40 mitochondrial single nucleotide polymorphisms in 7219 Framingham Heart Study participants. The nonsynonymous mitochondrial single nucleotide polymorphism 5913G>A (Asp4Asn) in the cytochrome c oxidase subunit 1 of respiratory complex IV demonstrated significant associations with BP and fasting blood glucose (FBG) levels. Individuals with the rare 5913A allele had, on average, 7-mm Hg higher systolic BP at baseline (
P
empirical
=0.05) and 17-mg/dL higher mean FBG over 25 years of follow-up (
P
empirical
=0.009). Significant associations with FBG levels were also detected for nonsynonymous mitochondrial single nucleotide polymorphism 3316G>A (Ala4Thr) in the NADH dehydrogenase subunit 1 of complex I. On average, individuals with rare allele 3316A had 17- and 25-mg/dL higher FBG at baseline (
P
empirical
=0.01) and over 25 years of follow-up (
P
empirical
=0.007). Our findings provide the first evidence of putative association of variants in the mitochondrial genome with systolic BP and FBG in the general population. Replication in independent samples, however, is needed to confirm these putative associations.
Aldosterone Acting Through the Central Nervous System Sensitizes Angiotensin II-Induced Hypertension
Authors: Xue Baojian , Zhang Zhongming , Roncari Camila F. , Guo Fang , Johnson Alan Kim
Published: September 2012

Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other’s pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction–delay–expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin–angiotensin–aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca
2+
]
i
after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.
G protein receptor kinase 4 polymorphisms
Authors: Vandell Alexander G. , Lobmeyer Maximilian T. , Gawronski Brian E. , Langaee Taimour Y. , Gong Yan , Gums John G. , Beitelshees Amber L. , Turner Stephen T. , Chapman Arlene B. , Cooper-DeHoff Rhonda M. , Bailey Kent R. , Boerwinkle Eric , Pepine Carl J. , Liggett Stephen B. , Johnson Julie A.
Published: September 2012

G protein–coupled receptor kinases (GRKs) are important regulatory proteins for many G protein–coupled receptors, but little is known about
GRK4
pharmacogenetics. We hypothesized that 3 nonsynonymous
GRK4
single-nucleotide polymorphisms, R65L (rs2960306), A142V (rs1024323), and A486V (rs1801058), would be associated with blood pressure response to atenolol, but not hydrochlorothiazide, and would be associated with long-term cardiovascular outcomes (all-cause death, nonfatal myocardial infarction, nonfatal stroke) in participants treated with an atenolol-based versus verapamil-SR–based antihypertensive strategy.
GRK4
single-nucleotide polymorphisms were genotyped in 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) trial. In whites and blacks, increasing copies of the variant 65L-142V haplotype were associated with significantly reduced atenolol-induced diastolic blood pressure lowering (−9.1±6.8 versus −6.8±7.1 versus −5.3±6.4 mm Hg in participants with 0, 1, and 2 copies of 65L-142V, respectively;
P
=0.0088). One thousand four hundred sixty participants with hypertension and coronary artery disease from the INternational VErapamil SR/Trandolapril STudy (INVEST) were genotyped, and variant alleles of all 3
GRK4
single-nucleotide polymorphisms were associated with increased risk for adverse cardiovascular outcomes in an additive fashion, with 486V homozygotes reaching statistical significance (odds ratio, 2.29 [1.48–3.55];
P
=0.0002). These effects on adverse cardiovascular outcomes were independent of antihypertensive treatment. These results suggest that the presence of
GRK4
variant alleles may be important determinants of blood pressure response to atenolol and risk for adverse cardiovascular events. The associations with GRK4 variant alleles were stronger in patients who were also
ADRB1
389R homozygotes, suggesting a potential interaction between these 2 genes.
Inhaled Nitric Oxide Reduces Brain Damage by Collateral Recruitment in a Neonatal Stroke Model
Authors: Charriaut-Marlangue Christiane , Bonnin Philippe , Gharib Abdallah , Leger Pierre-Louis , Villapol Sonia , Pocard Marc , Gressens Pierre , Renolleau Sylvain , Baud Olivier
Published: September 2012

Background and Purpose—

We recently demonstrated that endogenous nitric oxide (NO) modulates collateral blood flow in a neonatal stroke model in rats. The inhalation of NO (iNO) has been found to be neuroprotective after ischemic brain damage in adults. Our objective was to examine whether iNO could modify cerebral blood flow during ischemia–reperfusion and reduce lesions in the developing brain.

Methods—

In vivo variations in cortical NO concentrations occurring after 20-ppm iNO exposure were analyzed using the voltammetric method in P7 rat pups. Inhaled NO-mediated blood flow velocities were measured by ultrasound imaging with sequential Doppler recordings in both internal carotid arteries and the basilar trunk under basal conditions and in a neonatal model of ischemia–reperfusion. The hemodynamic effects of iNO (5 to 80 ppm) were correlated with brain injury 48 hours after reperfusion.

Results—

Inhaled NO (20 ppm) significantly increased NO concentrations in the P7 rat cortex and compensated for the blockade of endogenous NO synthesis under normal conditions. Inhaled NO (20 ppm) during ischemia increased blood flow velocities and significantly reduced lesion volumes by 43% and cellular damage. In contrast, both 80 ppm iNO given during ischemia and 5 or 20 ppm iNO given 30 minutes after reperfusion were detrimental.

Conclusions—

Our findings strongly indicate that, with the appropriate timing, 20 ppm iNO can be transported into the P7 rat brain and mediated blood flow redistribution during ischemia leading to reduced infarct volume and cell injury.
Effect of Focal Ischemia on Long Noncoding RNAs
Authors: Dharap Ashutosh , Nakka Venkata Prasuja , Vemuganti Raghu
Published: September 2012

Background and Purpose—

Long noncoding RNAs (lncRNAs) play a significant role in cellular physiology. We evaluated the effect of focal ischemia on the expression of 8314 lncRNAs in rat cerebral cortex using microarrays.

Methods—

Ischemia was induced by transient middle cerebral artery occlusion. Genomic and transcriptomic correlates of the stroke-responsive lncRNAs and the transcription factor binding sties in their promoters were evaluated with bioinformatics.

Results—

Three hundred fifty-nine lncRNAs were upregulated (>2-fold) and 84 were downregulated (<0.5-fold) at 3 hours to 12 hours of reperfusion after middle cerebral artery occlusion compared with sham. Sixty-two stroke-responsive lncRNAs showed >90% sequence homology with exons of protein-coding genes. Promoters of stroke-responsive lncRNA genes and their homologous protein-coding genes showed highly overlapping transcription factor binding sites. Despite presence of open reading frames, lncRNAs did not form any product when subjected to in vitro translation.

Conclusions—

Stroke significantly alters cerebral lncRNA expression profiles.
Arterial Stiffness and Progressive Neurological Deficit in Patients With Acute Deep Subcortical Infarction
Authors: Saji Naoki , Kimura Kazumi , Kawarai Toshitaka , Shimizu Hirotaka , Kita Yasushi
Published: September 2012

Background and Purpose—

The mechanism of progressive neurological deficit (PND) in patients with ischemic stroke remains unclear. The aim of this study was to clarify whether arterial stiffness, a marker of vascular endothelial impairment and arteriosclerosis, is associated with PND in patients with acute deep subcortical infarction.

Methods—

We evaluated 156 consecutive first-ever ischemic stroke patients with acute deep subcortical infarction. PND was defined as an increment of ≥2 points in the National Institute of Health Stroke Scale score or an increase of ≥1 point in the limb weakness score within 7 days of stroke onset. Patients were assessed for risk factors, and infarct size was measured on initial diffusion-weighted magnetic resonance imaging. We measured brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness. We divided patients into 2 groups according to the presence or absence of PND to compare their clinical characteristics.

Results—

Fifty-two patients (33%) had PND, and baPWV was significantly higher in patients with than in those without PND. The baPWV cut-off value for PND was 18.24 m/s, with 90% sensitivity and 47% specificity. In multivariable logistic regression analysis, high baPWV (≥18.24 m/s; odds ratio, 8.22; 95% confidence interval, 2.55–31.9), large infarct size (≥15 mm; odds ratio, 2.76; 95% confidence interval, 1.01–7.92), and ≥3 infarct slices on serial axial diffusion-weighted imaging (odds ratio, 3.38; 95% confidence interval, 1.22–10.0) were independently associated with PND.

Conclusions—

Arterial stiffness indicated by baPWV is independently associated with PND in patients with acute deep subcortical infarction.
Applicability of the Normalized Difference Vegetation Index (NDVI) in Index-Based Crop Insurance Design
Authors: Turvey Calum G. , Mclaurin Megan K.
Published: September 2012

Index insurance is becoming increasingly popular because of its ability to provide low-cost, relatively easy to implement agricultural insurance for vegetation types whose productivity has been notoriously difficult to measure and to farmers in less-developed nations where traditional crop insurance schemes are not reasonable to implement. This study examines if the remotely sensed normalized difference vegetation index (NDVI) can be an effective basis for index-based crop insurance over a diverse set of locations. To do this the authors compare Advanced Very High Resolution Radiometer (AVHRR) values to cumulative precipitation, extreme heat, and crop yields for 60 locations across the United States for the years 1982–2003. Quadratic regression equations are used to explore these relationships. The findings suggest that the relationship between NDVI, precipitation, extreme heat, and crop yields is highly variable and dependent on location-specific characteristics. Without site-specific calibration, NDVI should not be widely applied to index-based insurance product design. However, NDVI may still be a useful tool in insurance design under certain circumstances. This may be disappointing to proponents of NDVI as a risk transfer mechanism but the authors believe it important to report negative results as a caveat, and to give researchers and practitioners pause before investing time and money into the proposition.
Effect of Transradial Coronary Angiography Procedure on Vascular Diameter and Vasodilator Functions in the Access Site
Authors: Okuyan Hizir , Açikgoz Sadik Kadri , Tacoy Gulten , Kocaman Sinan Altan , Abaci Adnan
Published: September 2012

The present study aimed to investigate the long-term effects of transradial procedures on the radial artery diameter and vasodilator properties. The study included a total of 35 patients (28 males and 7 females) who underwent left transradial coronary angiography with an appropriate indication. The radial artery diameters were measured before and after flow-mediated vasodilation (FMD) and nitrate-mediated vasodilation (NMD). The nonintervened right radial artery served as the control. A marked narrowing in the diameter of the intervened radial artery and impaired FMD response indicating endothelial dysfunction were observed at a mean of 9 months after transradial intervention. Structural and functional changes should be taken into consideration if previously intervened radial artery would be used for interventions, such as arterial bypass graft or dialysis fistula.
Physical activity and psychological distress amongst Vietnamese living in the Mekong Delta
Authors: Rees Susan , Silove Derrick , Chey Tien , Steel Zachary , Bauman Adrian , Phan Thuy
Published: September 2012

Objective:

Regular physical activity may be an important contributor to psychological well-being. This link has not been explored in ethnically distinct, low- and middle-income countries (LMIC), especially in countries affected by war. This study aimed to examine the relationship between physical activity and levels of psychological distress in an epidemiological cross-representative sample of Vietnamese living in the Mekong Delta region of Vietnam.

Methods:

The sample was drawn from an urban (Cần Thơ City) and a rural (Hậ u Giang) region, using a multi-stage probabilistic cluster sampling frame. The measures applied included the Composite International Diagnostic Interview (CIDI 2.0) yielding 12-month prevalence rates of common mental disorders, including anxiety, mood and substance use disorders; the Phan Vietnamese Psychiatric Scale (PVPS), a culturally specific self-report measure; and the Harvard Trauma Questionnaire. The Global Physical Activity Questionnaire (GPAQ version 1) was used to measure activity. Analyses were conducted using SAS software v.9.1.3. The population was assigned to three (high, moderate and low) physical activity levels. Analyses included chi-square tests and univariable and multivariable logistic models.

Results:

Physical activity was greater in males, the middle-aged group (30–54 years), those who were married, the rural population, less educated individuals and those who were employed. High physical activity was significantly associated with low levels of psychological distress (indexed by a combination of CIDI and PVPS cases identified) when controlling for socio-demographic factors and number of medical conditions). Membership of the lowest of the three physical activity groups was associated with a psychological distress odds ratio of 2.19 (95% CI 1.28–3.75). The results remained consistent when analyses were undertaken separately for males and females.

Conclusions:

Low levels of physical activity appear to be associated with greater psychological distress in the Mekong Delta of Vietnam. The association remained after adjusting for the influence of socio-demographic characteristics, exposure to past trauma, urban–rural residency and the presence of self-reported physical disorders. These data provide a foundation for exploring the role of physical activity as an adjunct to conventional interventions for common mental disorders in resource-poor LMIC countries.
Explaining Left–Right Party Congruence Across European Party Systems
Authors: Belchior Ana Maria
Published: September 2012

Empirical studies on representation have been based mainly on the descriptive analysis of levels of political or ideological congruence between MPs and voters. Very few studies focus on explaining congruence, and those that have done so do not explore all the explanatory dimensions. This article contributes to filling this gap by testing whether three theoretical models can explain left–right congruence among European parties. These models explore causality at the micro or individual level (the characteristics of voters and MPs), the meso level (party characteristics), and the macro or system level (party system and institutional characteristics). Based on data from the PIREDEU project, the study examines the party systems of the 27 countries of the European Union with reference to the 2009 European Parliament elections. The findings reveal that MP–voter congruence is best explained at the party level and by key MP candidate characteristics.
‘Why Should We Have to Prove We’re Alright?’: Counter-terrorism, Risk and Partial Securities
Authors: Mythen Gabe , Walklate Sandra , Khan Fatima
Published: September 2012

Under the auspices of the ‘war against terrorism’, New Labour’s period of political governance in the UK was characterized by an activist, pre-emptive approach to (inter)national security. This approach was domestically embedded in specific counter-terrorism measures such as extensions to detention without charge, the expansion of stop and search measures and the deployment of control orders. Situated in this context, this article analyses the reflections of a group of young British Pakistani Muslims living in the north-west of England. First, we detail the process of risk subjectification through which institutional labelling narrowly defines Muslims as threatening and dangerous. Second, we consider the consolidation of practices of self-surveillance through which young Muslims seek to protect themselves and deflect stigmatization. In conclusion, we suggest that counter-terrorism policies have succeeded in reproducing a state of partial securities in and through which certain groups are protected and ‘others’ exposed to scrutiny and hostility.
Keeping it Real? Social Class, Young People and ‘Authenticity’ in Reality TV
Authors: Allen Kim , Mendick Heather
Published: September 2012

In this article, we offer an empirical contribution to complement cultural analyses of social class-making in Reality Television (RTV). We draw on qualitative interviews with young people in England (aged 14–19). Analysing these discursively, we explore how young people take up, resist and rework discourses of ‘authenticity’ within RTV shows including The Apprentice and The X Factor. We conceptualise young people’s talk about RTV as performative, part of their ‘identity work’ through which they position themselves and others, and as embedded in wider processes of social distinction. We show that young people reject RTV contestants who are seen as too authentic in order to construct themselves as ordinary and thus normalise middle-classness. However, despite inviting audiences to make classed moral judgements, RTV provokes multiple readings. Specifically, some, mainly working-class, young people reject dominant discourses that pathologise working-class RTV contestants and instead value their lack of pretentiousness.
Vacationing in a Terror-Stricken Destination
Authors: Fuchs Galia , Uriely Natan , Reichel Arie , maoz Darya
Published: September 2012

This exploratory study examines the destination risk perceptions and risk rationalizations of tourists who, despite governmental travel advisories, cross the border into a region previously and repeatedly targeted by terror attacks. Data were collected from Israeli tourists at the Israeli–Egyptian border in Eilat on their way to the Sinai Desert. A statistical analysis of 489 questionnaires indicated that “terrorism and security” issues constituted only one dimension of tourists’ perceived risk among several others. The tourists used numerous means of rationalization to justify their seemingly irrational behavior, such as blaming the media for overexposure of terror risks. Finally, the respondents’ risk perceptions were found to be correlated with their political orientation regarding the Israeli-Arab conflict. Further investigations in other areas of conflict, as well as among tourists of different cultures, are recommended.
Serve, Nudge, and Share
Authors: Joaquin M. Ernita
Published: September 2012

The following is a review of John Clayton Thomas’ book Citizen, Customer, Partner: Engaging the Public in Public Management. This review examines the book’s guidelines to managers on the public’s three roles in administration.
Improving the Quality of Surveys of Physicians and Medical Groups
Authors: Klabunde Carrie N. , Willis Gordon B. , McLeod Caroline C. , Dillman Don A. , Johnson Timothy P. , Greene Sarah M. , Brown Martin L.
Published: September 2012

Because health care providers have a central role in implementing guidelines, health care reform, and new standards of care and technologies, surveying them about their practices and perspectives is vital for health services and policy research. In November 2010, the National Cancer Institute convened a workshop to review and discuss current methodologies in designing and fielding large-scale surveys of physicians and medical groups. This report summarizes key issues and future directions for four topic areas addressed in the workshop: sample frames for surveying physicians and medical groups; points of contact and response modes; response incentives; and questionnaire design and burden. Recommendations were made for improving sample frame databases, optimizing mixed-mode surveys, and studying use of incentives with gatekeepers and in medical group settings. There is particular need for empirical assessment of factors that motivate or impede participation of physicians, other types of clinicians, and medical groups in survey research.
The Women and Work Commission legacy in the age of austerity
Authors: Ward Rosalie
Published: September 2012

In 2006 the UK Women and Work Commission found that significant pay inequalities between men and women in the workplace continued. Many of the contributory factors were complex but, crucially, occupational segregation, lack of vocational qualifications, discrimination and fewer quality job opportunities enabling women to combine their work and care roles, needed to be addressed in order to close the gender pay gap. Through the viewpoint of three senior women trade unionists, this article examines the findings and recommendations of the UK Women and Work Commission as set out in the first report 2006 and final report 2009. It assesses the progress made against the final recommendations and discusses the impact that the change in government policy direction, with its focus on deficit reduction, is having on closing the gender pay gap.
Building safer robots: Safety driven control
Authors: Woodman Roger , Winfield Alan F.T. , Harper Chris , Fraser Mike
Published: September 2012

In recent years there has been a concerted effort to address many of the safety issues associated with physical human–robot interaction (pHRI). However, a number of challenges remain. For personal robots, and those intended to operate in unstructured environments, the problem of safety is compounded. In this paper we argue that traditional system design techniques fail to capture the complexities associated with dynamic environments. We present an overview of our safety-driven control system and its implementation methodology. The methodology builds on traditional functional hazard analysis, with the addition of processes aimed at improving the safety of autonomous personal robots. This will be achieved with the use of a safety system developed during the hazard analysis stage. This safety system, called the safety protection system, will initially be used to verify that safety constraints, identified during hazard analysis, have been implemented appropriately. Subsequently it will serve as a high-level safety enforcer, by governing the actions of the robot and preventing the control layer from performing unsafe operations. To demonstrate the effectiveness of the design, a series of experiments have been conducted using a MobileRobots PeopleBot. Finally, results are presented demonstrating how faults injected into a controller can be consistently identified and handled by the safety protection system.
Visual navigation of a mobile robot with laser-based collision avoidance
Authors: Cherubini Andrea , Chaumette François
Published: September 2012

In this paper, we propose and validate a framework for visual navigation with collision avoidance for a wheeled mobile robot. Visual navigation consists of following a path, represented as an ordered set of key images, which have been acquired by an on-board camera in a teaching phase. While following such a path, the robot is able to avoid obstacles which were not present during teaching, and which are sensed by an on-board range scanner. Our control scheme guarantees that obstacle avoidance and navigation are achieved simultaneously. In fact, in the presence of obstacles, the camera pan angle is actuated to maintain scene visibility while the robot circumnavigates the obstacle. The risk of collision and the eventual avoiding behaviour are determined using a tentacle-based approach. The framework can also deal with unavoidable obstacles, which make the robot decelerate and eventually stop. Simulated and real experiments show that with our method, the vehicle can navigate along a visual path while avoiding collisions.
Long-Term Neurodevelopmental Follow-Up of Children With Congenital Muscular Torticollis
Authors: Schertz Mitchell , Zuk Luba , Green Dido
Published: September 2012

Congenital muscular torticollis is a common condition, but long-term neurodevelopmental follow-up is lacking. This study reports on neurodevelopmental outcome of 68 children, aged 7 to 9 years, with a history of congenital muscular torticollis, excluding children with torticollis due to other conditions. Thirty-eight children were examined for presence of neurodevelopmental disorders. Telephone interview data were available for an additional 30 children. Of those examined, 22/38 (57.9%) had or were at risk for a developmental disorder (attention-deficit hyperactivity disorder (ADHD), developmental coordination disorder, language impairment, autistic spectrum disorder) on at least 1 of the assessments administered, 23/38 (60.5%) had received developmental treatment during childhood. One child, based on a telephone interview, had a history of developmental treatment. Therefore, 30/68 (44.1%) children of the total sample demonstrated a developmental delay/disorder, currently (22/68) or previously (8/68). Our findings suggest congenital muscular torticollis to be a significant risk factor for later neurodevelopmental conditions with disorders presenting at different stages of development.
Parent and Self-Report Health-Related Quality of Life Measures in Young Patients With Tourette Syndrome
Authors: Cavanna Andrea E. , Luoni Chiara , Selvini Claudia , Blangiardo Rosanna , Eddy Clare M. , Silvestri Paola R. , Cali’ Paola V. , Gagliardi Emanuela , Balottin Umberto , Cardona Francesco , Rizzo Renata , Termine Cristiano
Published: September 2012

Tourette syndrome is a neurodevelopmental disorder characterized by tics and comorbid behavioral problems. This study compared child- and parent-reported quality of life and everyday functioning. We assessed 75 children with Tourette syndrome, of which 42 (56%) had comorbid conditions (obsessive-compulsive disorder = 25; attention-deficit hyperactivity disorder = 6; both comorbidities = 4). All patients completed psychometric instruments, including the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (child report) and the Child Tourette’s Syndrome Impairment Scale (parent report). Data were compared for patients with pure Tourette syndrome, Tourette syndrome + obsessive-compulsive disorder, Tourette syndrome + attention-deficit hyperactivity disorder, and Tourette syndrome + both comorbidities. There were no group differences in quality of life. However, there were differences for total, school, and home activities impairment scores. Children and parents may not share similar views about the impact of Tourette syndrome on functioning. The measurement of health-related quality of life in Tourette syndrome is more complex in children than adults.