bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Intake and Colorectal Cancer Risk by Molecularly Defined Subtypes in a Prospective Study of Older Women
Authors: Razzak Anthony A. , Oxentenko Amy S. , Vierkant Robert A. , Tillmans Lori S. , Wang Alice H. , Weisenberger Daniel J. , Laird Peter W. , Lynch Charles F. , Anderson Kristin E. , French Amy J. , Haile Robert W. , Harnack Lisa J. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul J.
Published: September 2011

Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor. However, existing data are less conclusive for women than men. Also, to date, relatively few studies have reported alcohol-related CRC risks based on molecularly defined tumor subtypes. We evaluated associations between alcohol intake and incident CRC, overall and by microsatellite instability [MSI high (MSI-H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status in the prospective, population-based Iowa Women's Health Study (IWHS; n = 41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were obtained by self-report. Incident CRCs were prospectively identified and archived, paraffin-embedded tissue specimens were collected from 732 representative cases, diagnosed through December 31, 2002. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9–292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less (RR = 1.00; 95% CI, 0.86–1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91–1.24) were not significantly associated with overall CRC risk. Analyses based on alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile distributions yielded similar risk estimates. Null associations were also observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined CRC subtypes (P > 0.05 for each comparison). These data do not support an adverse effect from alcohol intake on CRC risk, overall or by specific molecularly defined subtypes, among older women. Cancer Prev Res; 4(12); 2035–43. ©2011 AACR.
Conditioned Place Preference Associated with Level of Palmitoylation of PSD-95 in Rat Hippocampus and Nucleus Accumbens
Authors: Zhang Xiaojie , Liu Xuebing , Wang Daijun , Liu Haidan , Hao Wei
Published: September 2011

Psychostimulant-mediated synaptic plasticity in the hippocampus and nucleus accumbens is one of the pathological features of addiction, a disease of learning and memory. Dynamic palmitoylation of PSD-95 modulates synaptic plasticity, but its role in addiction is not fully understood. Using a morphine-conditioned place preference (CPP) rat model and Acyl-biotin exchange (ABE) labeling we found a correlation between CPP and levels of palmitoylated PSD-95 in the hippocampus and nucleus accumbens. Rats that developed significant CPP had higher levels of palmitoylation of PSD-95 in the hippocampus and nucleus accumbens. Furthermore, palmitoylation of PSD-95 was significantly decreased in the hippocampus but increased in the nucleus accumbens during the beginning of withdrawal. With long-term withdrawal, palmitoylated PSD-95 in these regions recovered, while CPP waned and physical signs gradually disappeared. However, morphine reinjection restored strong CPP without producing any significant changes in palmitoylation of PSD-95. Our findings suggest that CPP is correlated with the dynamics of PSD-95 palmitoylation in rat hippocampus and nucleus accumbens, and could be one of the mechanisms for morphine-dependent synaptic plasticity.
Event-Related Potential Study of Illusory Contour Perception in Schizophrenia
Authors: Ikeda Chisako , Kirino Eiji , Inoue Reiichi , Arai Heii
Published: September 2011

Schizophrenic patients and healthy controls participated in event-related potential experiments, in which illusory contour (IC) and control objects [no contour (NC), real contour (RC)] were passively presented. As a result, P100 latency for IC in schizophrenic patients was significantly prolonged (+10.6 ms) compared to those for RC. The present findings indicate that an abnormality of IC processing, including ‘bottom-up’ as well as ‘top-down’ processing, may reflect basal pathogenesis of various clinical representations of schizophrenia. However, the P100 latency difference between IC and RC was very small in the patient group. Rather, ‘cognitive’ in the Positive and Negative Syndrome Scale (PANSS) model of Bell et al. significantly correlated with P100 latencies for NC. Such an association between PANSS and NC processing, where the shape must be inferred with increased attentional demands and ‘top-down’ processing, indicates that the abnormality of schizophrenic patients’ preattentive process might be a problem of ‘top-down’ processing rather than ‘bottom-up’ processing.
The Value of Neonatal Autopsy
Authors: Hickey Leah , Murphy Amanda , Devaney Deirdre , Gillan John , Clarke Tom
Published: September 2011

Background and Objective: Neonatal autopsy rates were in decline internationally at the end of the last century. Our objective was to assess the current value of neonatal autopsy in providing additional information to families and healthcare professionals. Methods: We conducted a review of neonatal autopsies performed in a tertiary perinatal centre over an 11-year period. Primary outcomes measured were the annual neonatal autopsy rates and concordance rates between clinical and autopsy diagnoses of the primary cause of death. Secondary outcomes were the clinical, genetic and audit value of the examinations. Findings were used to inform the consent process, and the effect this had on institutional post-mortem rates was assessed over the subsequent 5-year period. Results: There was a marked decline in the annual neonatal autopsy rate from 73% in 1994 to 48% in 2004. 164 cases met the inclusion criteria for review. Complete concordance for cause of death was reached in 91% of cases. Previously unsuspected or unconfirmed clinical conditions, other than the primary cause of death, were uncovered at autopsy in 85 cases. Detailed information on inheritable conditions was obtained in 45 cases. Findings with perceived ‘audit value’ for clinical practice were identified in 29 cases. The dissemination of this information to staff and families contributed to the stabilisation of the consent rate in the following 5-year period. Conclusion: Neonatal autopsy remains a valuable diagnostic tool as it provides critical clinical and audit information for healthcare professionals and families.
Short-Term Outcome for Term and Near-Term Singleton Infants with Intrapartum Polyhydramnios
Authors: Leibovitch Leah , Schushan-Eisen Irit , Kuint Jacob , Weissmann-Brenner Alina , Maayan-Metzger Ayala
Published: September 2011

Objective: To evaluate rates of early short-term neonatal complications among term and near-term newborn infants with polyhydramnios. Methods: Retrospective data were collected on 788 term infants with prenatal diagnosis of polyhydramnios and 1,576 matched controls, including information on maternal condition and on infant perinatal complications. Results: The total rate of major congenital malformations among infants born to mothers with polyhydramnios was 2.3% compared to 0.13% for those with normal amniotic fluid index (p < 0.001). Infants in the study group were more likely to be born to diabetic mothers, were heavier and large for gestational age and were more likely to be delivered by cesarean section. Infants with polyhydramnios, but no major congenital malformations, are at increased risk for minor congenital malformations (4.2%) as well as for postnatal complications, such as respiratory distress (5.7%), cardiovascular manifestations (mainly delayed closure of the ductus arteriosus; 3.1%) and hypoglycemia (7%) compared to controls. Multivariate logistic regression revealed that polyhydramnios was associated only with postnatal respiratory distress and hypoglycemia. The severity of polyhydramnios was not associated with an increased rate of neonatal complications. Conclusion: Although infants with polyhydramnios, but no major congenital malformations, were found to have increased rates of respiratory distress and hypoglycemia, these clinical manifestations were mild and had little effect on the babies’ well-being and length of hospital stay.
The Effect of Postischemic Hypothermia on Apoptotic Cell Death in the Neonatal Rat Brain
Authors: Askalan Rand , Wang Carol , Shi Hui , Armstrong Edward , Yager Jerome Y.
Published: September 2011

Background and Objective: Hypothermia is the most effective neuroprotective therapy against ischemic injury in the developing brain. However, the mechanism of hypothermic neuroprotection is not well understood. We sought to investigate whether hypothermia mediates neuroprotection by modulating ischemia-induced apoptosis. Methods: Seven-day-old rat pups were randomly assigned to either control or hypoxia-ischemia (HI) groups. In the HI group, the internal carotid artery was ligated and cut. This was followed by transient hypoxia at 8% oxygen for 90 min. In the control rats, the internal carotid was isolated but not ligated. Immediately after the hypoxic episode, pups in the HI group were either placed in water baths maintained at 28°C for 24 h (core temperatures at 31°C) or they remained in a normothermic environment. Animals were sacrificed at 24, 48 and 72 h and 1 week after the HI insult. Brain sections were processed for immunohistochemistry and Western blots. Results: Caspase 3 expression was significantly higher in the core compared with the peri-infarct area at all time points in normothermic rats. Hypothermia reduced caspase 3 expression in the core but had little effect in the peri-infarct area. Hypothermia reduced apoptosis-inducing factor translocation to the nucleus in the core and peri-infarct area. Concurrently, X-linked inhibitor of apoptosis (XIAP) expression was significantly potentiated in the hypothermic-ischemic core but not in the peri-infarct area. Conclusion: Hypothermic modulation of caspase-dependent apoptosis may be mediated by upregulating XIAP. However, the effect of hypothermia on caspase-independent apoptosis may be mediated by XIAP-independent mechanisms. Importantly, these effects are mediated in both the core and the penumbral regions of ischemic lesion.
Severity of Mitral Stenosis and Left Ventricular Mechanics: A Speckle Tracking Study
Authors: Bilen Emine , Kurt Mustafa , Tanboga Ibrahim Halil , Kaya Ahmet , Isik Turgay , Ekinci Mehmet , Can Mehmet Mustafa , Karakas Mehmet Fatih , Oduncu Vecih , Bayram Ednan , Aksakal Enbiya , Sevimli Serdar
Published: September 2011

Background: It has been shown that mitral stenosis (MS) impairs left ventricular (LV) systolic function; however, this issue has not been studied comprehensively. We aimed to evaluate the role of 2D strain in the assessment of subclinical LV systolic dysfunction in patients with MS. Methods: Seventy-two patients with isolated MS (mild, moderate and severe) and 31 healthy control subjects constituted the study population. 2D echocardiography images were obtained from LV apical 4-chamber (4C), long axis (LAX), and 2-chamber (2C) views. Peak longitudinal strain and strain rate (Sr) were obtained from 4C, LAX, and 2C views. Global strain and Sr were calculated by averaging the three apical views. Results: There were no significant differences in LV ejection fraction and LV systolic or diastolic dimensions between the groups. Patients with MS had significantly lower LV longitudinal strain and Sr measurements than the control group. In addition, there were no significant differences in MS subgroups with respect to LV strain and Sr measurements. Conclusion: We demonstrated that patients with MS had lower LV functions using 2D strain imaging, and this is independent of the hemodynamic severity of MS. In the detection of subclinical LV dysfunction in patients with MS, 2D strain imaging appears to be useful.
Clinical and Pathological Features of Breast Cancer Associated with the Pathological Complete Response to Anthracycline-Based Neoadjuvant Chemotherapy
Authors: Keskin Serkan , Muslumanoglu Mahmut , Saip Pinar , Karanlık Hasan , Guveli Murat , Pehlivan Esmehan , Aydoğan Fatma , Eralp Yesim , Aydıner Adnan , Yavuz Ekrem , Ozmen Vahit , Igci Abdullah , Topuz Erkan
Published: September 2011

Objective: Patients with breast cancer with a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis than patients with residual disease. The aim of the current study was to identify predictors of pCR. Methods: This retrospective study included 388 patients treated with anthracycline-based NAC. Clinicopathological parameters were compared between the patients with and without pCR in breast and axilla. Results: Treatment consisted of FAC/FEC in 230 patients (59%), TAC in 39 (10%) patients and AC followed by docetaxel in 119 (31%). In all, 36 (9.3%) patients had pCR. In univariate analysis, age, tumor size, lymph node involvement, tumor grade (p = 0.077, n = 265), ER and HER-2 status (n = 213), lymphovascular invasion (LVI), type of chemotherapy and taxane-containing chemotherapy were associated with pCR. In multivariate analysis, ER negativity (p = 0.003), the absence of LVI (p = 0.009) and taxane-containing NAC (p = 0.026) were found to be significant indicators of pCR. Median follow-up time was 69 months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001). Conclusions: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy.
The Impact of 10% α-Hydroxy Acid Emulsion on Skin pH
Authors: Schreml S. , Meier R.J. , Albert M.G. , Seidl U. , Zeller V. , Behm B. , Landthaler M. , Abels C. , Babilas P.
Published: September 2011

Background/Aims: The effects of a 10% α-hydroxy acid (AHA) oil/water (O/W) emulsion on the pH of human skin surface (pHss) and stratum corneum (SC; pHsc) were evaluated in vivo. Methods: The AHA O/W emulsion was applied to an area on the volar forearm of male volunteers (n = 12), and then wiped off after 10 min. Prior to application and over the following 3 h, the pHss was measured. We used glass electrode measurements and time domain dual lifetime referencing (tdDLR) with luminescent sensor foils. In another experiment (n = 5), the impact of the AHA O/W emulsion on the pHsc gradient was measured by tape stripping of the SC of the volar forearm after application of the AHA O/W emulsion. Results: Compared with pHss values prior to treatment [5.2 ± 1.7 (tdDLR) or 4.8 ± 0.5 (electrode)], the pHss was significantly reduced 10 min after application [4.0 ± 0.3 (tdDLR) or 4.1 ± 0.1 (electrode)] and the pHss remained significantly reduced over the measurement period of 3 h [after 3 h: 4.4 ± 0.2 (tdDLR) or 4.5 ± 0.3 (electrode)]. The AHA O/W emulsion significantly reduced the pHsc even down to deep layers of the SC. Conclusion: After a 10-min application time, the 10% AHA O/W emulsion reduces the pHss (for at least 3 h) and pHsc in deep layers of the SC.
Effects of Monounsaturated Fatty Acids on Glycaemic Control in Patients with Abnormal Glucose Metabolism: A Systematic Review and Meta-Analysis
Authors: Schwingshackl L. , Strasser B. , Hoffmann G.
Published: September 2011

Background/Aims: In 2008, the American Diabetes Association recommended low-carbohydrate or low-fat diets for weight management in patients with established type 2 diabetes (T2D), while the amount of monounsaturated fatty acids (MUFA) was not specified. This systematic review focused on the effects of diets high in MUFA versus diets low in MUFA on important risk factors of T2D (i.e. plasma glucose, insulin, homeostasis model assessment of insulin resistance and glycosylated haemoglobin, HbA1c). Methods: Nine randomized controlled intervention trials with a total of 1,547 participants and a running time of at least 6 months, comparing diets high versus low in MUFA among adults with abnormal glucose metabolism (T2D, impaired glucose tolerance and insulin resistant), being overweight or obese, have been included in the meta-analysis. We performed a random effects meta-analysis to determine the weighted mean differences with 95% confidence intervals using the software package Review Manager 5.0.25 of the Cochrane Collaboration. Results: Significant differences in HbA1c were found (weighted mean difference –0.21%, 95% CI –0.40 to –0.02; p = 0.03), favouring the high MUFA groups. In contrast, fasting plasma glucose, fasting plasma insulin as well as the homeostasis model assessment of insulin resistance were not affected by the amounts of MUFA in the dietary protocols. Conclusions: In summary, this systematic review found that high MUFA diets appear to be effective in reducing HbA1c, and therefore, should be recommended in the dietary regimes of T2D.
Endothelial glycocalyx thickness and platelet-vessel wall interactions during atherogenesis
Authors: oude Egbrink Mirjam , Heijnen Viviane , Megens Remco , Engels Wim , Vink Hans , W. Slaaf Dick , van Zandvoort Marc , Reitsma Sietze
Published: September 2011

The endothelial glycocalyx (EG), the luminal cover of endothelial cells, is considered to be atheroprotective. During atherogenesis, platelets adhere to the vessel wall, possibly triggered by simultaneous EG modulation. It was the objective of this study to investigate both EG thickness and platelet-vessel wall interactions during atherogenesis in the same experimental model. Intravital fluorescence microscopy was used to study platelet-vessel wall interactions in vivo in common carotid arteries and bifurcations of C57bl6/J (B6) and apolipoprotein E knock-out (ApoE-/-) mice (age 7 – 31 weeks). At the same locations, EG thickness was determined ex vivo using two-photon laser scanning microscopy. In ApoE-/- bifurcations the overall median level of adhesion was 48 platelets/mm2 (interquartile range: 16 – 80), which was significantly higher than in B6 bifurcations (0 (0 – 16), p = 0.001). This difference appeared to result from a significant age-dependent increase in ApoE-/- mice, while no such change was observed in B6 mice. At the same time, the EG in ApoE-/- bifurcations was significantly thinner than in B6 bifurcations (2.2 vs. 2.5 μm, respectively; p < 0.05). This resulted from the fact that in B6 bifurcations EG thickness increased with age (from 2.4 μm in young mice to 3.0 μm in aged ones), while in bifurcations of ApoE-/- mice this growth appeared to be absent (2.2 μm at all ages). During atherogenesis, platelet adhesion to the wall of the carotid artery bifurcation increases significantly. At the same location, EG growth with age is hampered. Therefore, glycocalyx-reinforcing strategies could possibly ameliorate atherosclerosis.
Common variants in the haemostatic gene pathway contribute to risk of early-onset myocardial infarction in the Italian population
Authors: Guella Ilaria , Ardissino Diego , Merlini Pier , Peyvandi Flora , Mannucci Pier , Asselta Rosanna , Duga Stefano
Published: September 2011

Occlusive coronary thrombus formation superimposed on an atherosclerotic plaque is the ultimate event leading to myocardial infarction (MI). Therefore, haemostatic proteins may represent important players in the pathogenesis of MI. It was the objective of this study to evaluate, in a comprehensive way, the role of haemostatic gene polymorphisms in predisposition to premature MI. A total of 810 single nucleotide polymorphisms (SNPs) in 37 genes were assessed for association with MI in a large cohort (1,670 males, 210 females) of Italian patients who suffered from an MI event before the age of 45, and an equal number of controls. Thirty-eight SNPs selected from the literature were genotyped using the SNPlex technology, whereas genotypes for the remaining 772 SNPs were extracted from a previous genome-wide association study. Genotypes were analysed by a standard case-control analysis corrected for classical cardiovascular risk factors, and by haplotype analysis. A weighted Genetic Risk Score (GRS) was calculated. Evidence for association with MI after covariate correction was found for 35 SNPs in 12 loci: F5, PROS1, F11, ITGA2, F12, F13A1, SERPINE1, PLAT, VWF, THBD, PROCR, and F9. The weighted GRS was constructed by including the top SNP for each of the 12 associated loci. The GRS distribution was significantly different between cases and controls, and subjects in the highest quintile had a 2.69-fold increased risk for MI compared with those in the lowest quintile. Our results suggest that a GRS, based on the combined effect of several risk alleles in different haemostatic genes, is associated with an increased risk of MI.
Factor VIII activation by factor VIIa analog (V158D/E296V/M298Q) in tissue factor-independent mechanisms
Authors: Ogiwara Kenichi , Shima Midori , Nogami Keiji
Published: September 2011

Factor (F)VIIa with tissue factor (TF) is a primary trigger of blood coagulation. The recombinant (r)FVIIa analog, NN1731 (V158D/E296V/ M298Q) containing a thrombin/FIXa-mimicking catalytic domain, is ~30-fold more effective on activated platelets without TF, but ~1.2-fold with TF, than rFVIIa for FX activation. We have recently demonstrated the FVIIa/TF-dependent FVIII activation in the early coagulation phase. We assessed the action of NN1731 on FVIII activation. NN1731/TF increased FVIII activity ~2.9-fold within 30 seconds, followed by rapid inactivation, and was slightly more active than rFVIIa/TF. NN1731-catalysed activation, however, was enhanced ~6-fold at 5 minutes (min), and its peak level persisted for ~30 min. NN1731/TF proteolysed FVIII at Arg740, Arg372, and Arg336, similar to rFVIIa/TF, but cleavage by NN1731 alone was much slower at Arg336 than at Arg740 and Arg372. The Km and Vmax for NN1731/TF-catalysed activation were ~1.8-fold lower and ~2.3-fold greater than rFVIIa/TF. The Km for NN1731 alone was ~1.3-fold lower than rFVIIa, whilst the Vmax was ~7.9-fold greater, indicating that the efficiency of FVIII activation by NN1731 and NN1731/TF was ~11- and ~4-fold greater, respectively, than equivalent reactions with rFVIIa. In SPR-based assays, NN1731 bound to FVIII and the heavy chain (Kd; 0.62 and 1.9 nM) with ~1.4- and ~3.1-fold higher affinity than rFVIIa, and the A2 domain contributed to this increase. Von Willebrand factor moderated NN1731-catalysed activation more significantly than NN1731/TF. In conclusion, NN1731 was a greater potential than rFVIIa in up-regulating FVIII activity, and the TF-independent FVIII activation might represent a potential extra mode of its enhanced haemostatic effect.
The role of fibrinogen plasma levels, the –455G>A fibrinogen and the factor XIII A subunit (FXIII-A) Val34Leu polymorphism in cancer-associated venous thrombosis
Authors: Tiedje Vera , Dunkler Daniela , Ay Cihan , Horvath Birgit , Quehenberger Peter , Pabinger Magdalena , Zielinski Christoph , Mannhalter Christine , Pabinger Ingrid
Published: September 2011

Venous thromboembolism (VTE) is a life-threatening complication in cancer patients. Identification of risk factors has been in focus in the past years. Functional single nucleotide polymorphisms (SNP) of coagulation factors known to influence the concentration or function may be considered to influence the risk of VTE in cancer patients. We evaluated the influence of fibrinogen plasma levels, the –455G>A SNP in the fibrinogen beta gene and the Val34Leu (163G>T) SNP in the factor XIII A-subunit (FXIII-A) gene on the risk of VTE. In 1,079 tumour patients recruited for the prospective Vienna Cancer and Thrombosis Study (CATS) fibrinogen levels were determined by the Clauss method. The FXIII-A Val34Leu and the fibrinogen –455G>A SNPs were tested by allele-specific PCR. The median follow-up time was 604 days, 83 thrombotic events occurred. The median fibrinogen level was 381 mg/dl (25th-75th percentile: 312 to 467). In a multivariable Cox model adjusted to chemotherapy, surgery, radiotherapy, age and sex, neither the fibrinogen concentration (hazard ratio [HR] =1.05, confidence interval [CI] 0.839–1.310 p=0.68), nor the –455G>A SNP (HR=0.77, 95%CI 0.491–1.197; p=0.24), nor the Val34Leu SNP (HR=0.99, 95%CI 0.646–1.542 p=0.99) were associated with occurrence of VTE. The fibrinogen concentration was not significantly different among the fibrinogen –455G or A genotype carriers (p = 0.33). Disseminated intravascular coagulation was observed in only five patients, none of these developed VTE. In conclusion, fibrinogen plasma levels, the fibrinogen –455G>A and the FXIII-A Val34Leu polymorphisms were not associated with VTE in our study.
Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients
Authors: Gallagher Arlene , Setakis Efrosini , Plumb Jonathan , Clemens Andreas , van Staa Tjeerd-Pieter
Published: September 2011

Atrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral anticoagulation with warfarin can reduce this risk. The objective of this study was to evaluate the association between time in therapeutic International Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and mortality. The study cohort included AF patients aged 40 years and older included in the UK General Practice Research Database. For patients treated with warfarin we computed the percentage of follow-up time spent within therapeutic range. Cox regression was used to assess the association between INR and outcomes while controlling for patient demographics, health status and concomitant medication. The study population included 27,458 warfarintreated (with at least 3 INR measurements) and 10,449 patients not treated with antithrombotic therapy. Overall the warfarin users spent 63% of their time within therapeutic range (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc score. Patients who spent at least 70% of time within therapeutic range had a 79% reduced risk of stroke compared to patients with ≤30% of time in range (adjusted relative rate of 0.21; 95% confidence interval 0.18–0.25). Mortality rates were also significantly lower with at least 70% of time spent within therapeutic range. In conclusion, good anticoagulation control was associated with a reduction in the risk of stroke.
Feasibility of a Heart Failure Disease Management Program in Eastern Europe: Tbilisi, Georgia
Authors: Hebert Kathy , Quevedo Henry C. , Gogichaishvili Ilia , Nozadze Nino , Sagirashvili Ekaterine , Trahan Patrick , Kipshidze Nicholas , Arcement Lee M.
Published: September 2011

Background—

Little is known about the importation of a heart failure disease management program (HFDMP) into low- and middle-income countries. We examined the feasibility of importing a HFDMP into the country of Georgia, located in the Caucuses.

Methods and Results—

Patients with ejection fraction ≤40% were enrolled into a prospective, observational study consisting of a new HFDMP staffed by local cardiologists. Medications, emergency department use, hospital admissions, and mortality were assessed by interviews with patients or their families. Screening resulted in 400 patients who were followed for 10.2±3.5 months. β-Blocker prescriptions increased from 7.4–80.7% (
P
<0.001), angiotensin-converting enzyme inhibitor prescriptions increased from 18.4–92.6% (
P
<0.001), and mean systolic blood pressure declined from 145 to 114 mm Hg (
P
<0.001). Patients visiting the emergency department and hospitalizations were lowered by 40.7% and 52.5%, respectively, but were also influenced by the outbreak of war, during which 17.5% (n=70) of patients received follow-up in refugee tents. All-cause mortality extended to 7% of patients, with 12 of 28 deaths caused by war-related events.

Conclusions—

Importation of a Western HFDMP was demonstrated to be feasible, with a 5-fold increase in the use of recommended therapies, reduction of blood pressure, decrease of emergency department visits, and hospitalizations for heart failure. These measures could result in substantial cost savings in resource-limited settings, but assessment is complicated in unstable areas. Translating effective interventions to low- and middle-income countries requires sensitivity to regional cultures and flexibility to adapt both clinical goals and strategies to unexpected conditions.
Isoflavone Soy Protein Supplementation and Atherosclerosis Progression in Healthy Postmenopausal Women
Authors: Hodis Howard N. , Mack Wendy J. , Kono Naoko , Azen Stanley P. , Shoupe Donna , Hwang-Levine Juliana , Petitti Diana , Whitfield-Maxwell Lora , Yan Mingzhu , Franke Adrian A. , Selzer Robert H. ,   for the Women's Isoflavone Soy Health Research Group
Published: September 2011

Background and Purpose—

Although epidemiological and experimental studies suggest that dietary intake of soy may be cardioprotective, use of isoflavone soy protein (ISP) supplementation as a primary preventive therapy remains unexplored. We determined whether ISP reduces subclinical atherosclerosis assessed as carotid artery intima-media thickness progression.

Methods—

In a double-blind, placebo-controlled trial, 350 postmenopausal women 45 to 92 years of age without diabetes and cardiovascular disease were randomized to 2 evenly divided daily doses of 25 g soy protein containing 91 mg aglycon isoflavone equivalents or placebo for 2.7 years.

Results—

Overall, mean (95% CI) carotid artery intima-media thickness progression rate was 4.77 (3.39–6.16) μm/year in the ISP group and 5.68 (4.30–7.06) μm/year in the placebo group. Although carotid artery intima-media thickness progression was reduced on average by 16% in the ISP group relative to the placebo group, this treatment effect was not statistically significant (
P
=0.36). Among the subgroup of women who were randomized within 5 years of menopause, ISP participants had on average a 68% lower carotid artery intima-media thickness progression rate than placebo participants 2.16 (−1.10 to 5.43) versus 6.79 (3.56–10.01) μm/year (
P
=0.05). ISP supplementation had a null effect on women who were >5 years beyond menopause when randomized. There were no major adverse events from ISP supplementation.

Conclusions—

ISP supplementation did not significantly reduce subclinical atherosclerosis progression in postmenopausal women. Subgroup analysis suggests that ISP supplementation may reduce subclinical atherosclerosis in healthy young (median age, 53 years) women at low-risk for cardiovascular disease who were <5 years postmenopausal. These first trial results of their kind warrant further investigation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00118846.
Temporal and Spatial Variability of Great Lakes Ice Cover, 1973–2010*
Authors: Wang Jia , Bai Xuezhi , Hu Haoguo , Clites Anne , Colton Marie , Lofgren Brent
Published: September 2011

In this study, temporal and spatial variability of ice cover in the Great Lakes are investigated using historical satellite measurements from 1973 to 2010. The seasonal cycle of ice cover was constructed for all the lakes, including Lake St. Clair. A unique feature found in the seasonal cycle is that the standard deviations (i.e., variability) of ice cover are larger than the climatological means for each lake. This indicates that Great Lakes ice cover experiences large variability in response to predominant natural climate forcing and has poor predictability. Spectral analysis shows that lake ice has both quasi-decadal and interannual periodicities of ~8 and ~4 yr. There was a significant downward trend in ice coverage from 1973 to the present for all of the lakes, with Lake Ontario having the largest, and Lakes Erie and St. Clair having the smallest. The translated total loss in lake ice over the entire 38-yr record varies from 37% in Lake St. Clair (least) to 88% in Lake Ontario (most). The total loss for overall Great Lakes ice coverage is 71%, while Lake Superior places second with a 79% loss. An empirical orthogonal function analysis indicates that a major response of ice cover to atmospheric forcing is in phase in all six lakes, accounting for 80.8% of the total variance. The second mode shows an out-of-phase spatial variability between the upper and lower lakes, accounting for 10.7% of the total variance. The regression of the first EOF-mode time series to sea level pressure, surface air temperature, and surface wind shows that lake ice mainly responds to the combined Arctic Oscillation and El Niño–Southern Oscillation patterns.
Observing Local-Scale Variability of Near-Surface Temperature and Humidity Using a Wireless Sensor Network
Authors: Lengfeld Katharina , Ament Felix
Published: September 2011

In this paper the influence of surface type, wind speed, and other environmental conditions on near-surface air temperature, specific humidity, and surface temperature is studied. A wireless sensor network consisting of 13 low-cost meteorological stations was set up as a 2.3-km-long double transect in western Germany during the Fluxes and Patterns in the Soil–Vegetation–Atmosphere Scheme (FLUXPAT2009) campaign. This deployment covered various surface types, including a small river. It was found that the air temperature was mainly influenced by the distance to the river and that its variability is controlled by the wind speed. During the night, a pool of cold air formed in the valley close to the water. The specific humidity is also governed by proximity to the river, especially during the night and for low wind speeds. In contrast, the differences in surface temperature were caused by different land cover. These results can be confirmed by a cluster analysis. Setting up 13 stations in a relatively small area is not always feasible. In this study, an estimation of the error that is made by considering the effect of a reduced number of stations is given. Use of only a single station results in an error of 0.86 K in air temperature, 0.67 g kg−1 in specific humidity, and 1.4 K in surface temperature.
Routes of Transport across the Antarctic Polar Vortex in the Southern Spring
Authors: de la Cámara Alvaro , Mancho Ana M. , Ide Kayo , Serrano Encarna , Mechoso Carlos R.
Published: September 2011

Transport in the lower stratosphere over Antarctica has been studied in the past by means of several approaches, such as contour dynamics or Lyapunov exponents. This paper examines the problem by means of a new Lagrangian descriptor, which is referred to as the function M. The focus is on the southern spring of 2005, which allows for a comparison with previous analyses based on Lyapunov exponents. With the methodology based on the function M, a much sharper depiction of key Lagrangian features is achieved and routes of large-scale horizontal transport across the vortex edge are captured. These results highlight the importance of lobe dynamics as a transport mechanism across the Antarctic polar vortex.
Tropical Oceanic Hot Towers: Need They Be Undilute to Transport Energy from the Boundary Layer to the Upper Troposphere Effectively? An Answer Based on Trajectory Analysis of a Simulation of a TOGA COARE Convective System
Authors: Fierro Alexandre O. , Zipser Edward J. , LeMone Margaret A. , Straka Jerry M. , Simpson Joanne (Malkus)
Published: September 2011

This paper addresses questions resulting from the authors’ earlier simulation of the 9 February 1993 Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Research Experiment (TOGA COARE) squall line, which used updraft trajectories to illustrate how updrafts deposit significant moist static energy (in terms of equivalent potential temperature θe) in the upper troposphere, despite dilution and a θe minimum in the midtroposphere. The major conclusion drawn from this earlier work was that the “hot towers” that Riehl and Malkus showed as necessary to maintain the Hadley circulation need not be undilute. It was not possible, however, to document how the energy (or θe) increased above the midtroposphere. To address this relevant scientific question, a high-resolution (300 m) simulation was carried out using a standard 3-ICE microphysics scheme (Lin–Farley–Orville).

Detailed along-trajectory information also allows more accurate examination of the forces affecting each parcel’s vertical velocity W, their displacement, and the processes impacting θe, with focus on parcels reaching the upper troposphere. Below 1 km, pressure gradient acceleration forces parcels upward against negative buoyancy acceleration associated with the sum of (positive) virtual temperature excess and (negative) condensate loading. Above 1 km, the situation reverses, with the buoyancy (and thermal buoyancy) acceleration becoming positive and nearly balancing a negative pressure gradient acceleration, slightly larger in magnitude, leading to a W minimum at midlevels. The W maximum above 8 km and concomitant θe increase between 6 and 8 km are both due to release of latent heat resulting from the enthalpy of freezing of raindrops and riming onto graupel from 5 to 6.5 km and water vapor deposition onto small ice crystals and graupel pellets above that, between 7 and 10 km.
Zonal Jets as Meridional Transport Barriers in the Subtropical and Polar Lower Stratosphere
Authors: Beron-Vera Francisco J. , Olascoaga María J. , Brown Michael G. , Koçak Huseyin
Published: September 2011

Applications of recent results from dynamical systems theory to the study of transport and mixing in incompressible two-dimensional flows lead to the expectation that, independent of the background potential vorticity (PV) distribution, weakly perturbed zonal jets are associated with barriers that inhibit meridional transport. Here the authors provide evidence in support of this expectation based on the analysis of isentropic winds in the lower stratosphere as produced by the Canadian Middle Atmosphere Model (CMAM), a comprehensive general circulation model. Specifically, barriers to meridional transport are found to be associated with the (eastward) austral polar night jet, for which the meridional gradient of background PV is large, and also for the (westward) boreal summer subtropical jet, for which the background PV gradient is quite small. The identification of the meridional transport barriers is based on the computation of finite-time Lyapunov exponents (FTLEs), which characterize the amount of stretching about fluid particle trajectories. Being composed of regular fluid particle trajectories lying on invariant tori, the meridional transport barriers are identified with topologically circular, local minimizing curves or trenches of the backward-plus-forward FTLE field. Results from explicit passive tracer advection experiments and flux computations are also presented, which are consistent with results inferred using the FTLE diagnostic.
MJO Modulation on 2009/10 Winter Snowstorms in the United States*
Authors: Moon Ja-Yeon , Wang Bin , Ha Kyung-Ja
Published: September 2011

During the winter of 2009/10, a number of record-breaking snowfall events registered in the eastern United States are shown to have been modulated by the pulsation of tropical MJO through an atmospheric teleconnection pattern. The intraseasonal variability over the eastern subtropical Pacific near Mexico (the equatorial central Pacific) had reached the maximum (second largest) strength since 1979/80. From late December to mid-February, the convection over these two regions experienced a remarkable wet–dry–wet cycle; correspondingly, the daily snowfall over the eastern United States also exhibited a wet–dry–wet cycle. As the MJO convection reached the central Pacific, a teleconnection pattern extended to North America, resulting in a westward-tilted deep anomalous trough anchored over the eastern United States, producing a low-level pressure dipole anomaly with an anticyclone (cyclone) centered at the U.S. West (East) Coast. The convection over the Indian Ocean varied in phase with the central Pacific convection, reinforcing the extratropical atmospheric teleconnection pattern. As a result, the enhanced high-latitude cold air penetrated southward, affecting the central and eastern United States. Meanwhile, warmer moist air was transported from the tropical central Pacific by the existing El Niño through Mexico to the southern United States along with the upper-level subtropical westerly jet, which extended from the subtropical Pacific to the Atlantic Ocean. As such, the eastern United States was located in a convergence zone between the enhanced cold air from the high latitude and the warm, moist air supplied from the subtropics, resulting in favorable conditions for extremely heavy snowfall.
Impacts of SST Anomalies in the Agulhas Current System on the Regional Climate Variability
Authors: Nakamura Mototaka
Published: September 2011

The potential impact of the variability in the Agulhas Current system on the large-scale atmospheric state in the Southern Hemisphere is examined, using the monthly near-surface baroclinicity as the key parameter, for the period between September 1980 and August 2002. Dominant patterns of anomalous near-surface baroclinicity found from empirical orthogonal function (EOF) analyses in the region that includes most of the Agulhas Current system show a wide variety of anomaly patterns: some of which indicate spatial shifts in the position of the Agulhas Retroflection and/or Agulhas Return Current. Composited anomalies in various atmospheric fields, sea surface temperature, and the net surface heat flux at the air–sea boundary based on the signals in the EOFs suggest that sea surface temperature anomalies in the Agulhas Current system thermally force the atmosphere on the synoptic scale via modification of the near-surface baroclinicity in March and April and possibly in January and February as well.
Thermally Driven and Eddy-Driven Jet Variability in Reanalysis
Authors: Li Camille , Wettstein Justin J.
Published: September 2011

Two important dynamical processes influence the extratropical zonal wind field: angular momentum transport by the thermally direct Hadley circulation (thermal-driving T) and momentum flux convergence by atmospheric waves (eddies) that develop in regions of enhanced baroclinicity (eddy-driving E). The relationship between extratropical zonal wind variability and these driving processes is investigated using 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data. Indices representing the processes (iT and iE) are defined based on vertically integrated diabatic heating and meridional convergence of the meridional flux of zonal momentum by eddies, respectively. Zonal wind signatures associated with these indices are identified via composite analysis. In the Atlantic sector, zonal wind variability is mainly associated with momentum flux convergence by baroclinic eddies, supporting the established view that the Atlantic jet is primarily eddy driven. In the Pacific sector, zonal wind variability is associated with both driving processes, evidence that the Pacific jet is both thermally driven and eddy driven. The thermally driven Pacific signature reflects changes in jet strength (intensity and longitudinal extent) with some resemblance to the zonal wind anomalies of the Pacific–North America (PNA) pattern. The eddy-driven signature reflects a latitudinal shift of the jet exit region in both sectors that resembles the zonal wind anomalies of the North Atlantic Oscillation (NAO) or West Pacific (WP) patterns.
An Experimental Study of the Small-Scale Variability of Rainfall
Authors: Tokay Ali , Kurtuluş
Published: September 2011

Small-scale variability of rainfall has been studied employing six dual rain gauge sites at Wallops Island, Virginia. The rain gauge sites were separated between 0.4 and 5 km, matching the beamwidth of Tropical Rainfall Measuring Mission (TRMM) and Global Precipitation Measurement (GPM) precipitation radars. During a 2-yr observational period, over 7100 rainy samples were received at 5-min integration. A single gauge did not report as high as 67% of the time when at least one of the other gauges had rainfall in one of the seasons. Since rainfall from one of the six rain gauges is sufficient for the rainy footprint from a satellite, this demonstrates the common occurrence of the partial beamfilling. For the periods where all gauges were reporting rainfall, a single gauge had at most 13% difference from the areal average rainfall in one of the seasons. This suggests that at the spatial scale of 5 km, the variability caused by the rain gradient is relatively less important than the variability arising from a partially filled footprint. During the passage of frontal systems and tropical cyclones, the beam was filled by rain most of the time and this resulted in relatively higher correlation distances. The correlation distance had a sharp drop off from 45 km in moderately variable rainfall to 3 km in highly variable rainfall and ranged from 5 to 35 km between the different seasons. This demonstrates its highly variable nature. Considering temporal sampling, the monthly rainfall error was 35% and 73% for 3-hourly and twice-daily observations, respectively.
Operator-Split Runge–Kutta–Rosenbrock Methods for Nonhydrostatic Atmospheric Models
Authors: Ullrich Paul , Jablonowski Christiane
Published: September 2011

This paper presents a new approach for discretizing the nonhydrostatic Euler equations in Cartesian geometry using an operator-split time-stepping strategy and unstaggered upwind finite-volume model formulation. Following the method of lines, a spatial discretization of the governing equations leads to a set of coupled nonlinear ordinary differential equations. In general, explicit time-stepping methods cannot be applied directly to these equations because the large aspect ratio between the horizontal and vertical grid spacing leads to a stringent restriction on the time step to maintain numerical stability. Instead, an A-stable linearly implicit Rosenbrock method for evolving the vertical components of the equations coupled to a traditional explicit Runge–Kutta formula in the horizontal is proposed. Up to third-order temporal accuracy is achieved by carefully interleaving the explicit and linearly implicit steps. The time step for the resulting Runge–Kutta–Rosenbrock–type semi-implicit method is then restricted only by the grid spacing and wave speed in the horizontal. The high-order finite-volume model is tested against a series of atmospheric flow problems to verify accuracy and consistency. The results of these tests reveal that this method is accurate, stable, and applicable to a wide range of atmospheric flows and scales.