bluuebunny/crossref_metadata_2025 huggingface dataset:
Subthreshold Sodium Current Underlies Essential Functional Specializations at Primary Auditory Afferents
Authors: Curti Sebastián , Gómez Leonel , Budelli Ruben , Pereda Alberto E.
Published: January 2008

Primary auditory afferents are generally perceived as passive, timing-preserving lines of communication. Contrasting this view, identifiable auditory afferents to the goldfish Mauthner cell undergo potentiation of their mixed—electrical and chemical—synapses in response to high-frequency bursts of activity. This property likely represents a mechanism of input sensitization because they provide the Mauthner cell with essential information for the initiation of an escape response. Consistent with this synaptic specialization, we show here that these afferents exhibit an intrinsic ability to respond with bursts of 200–600 Hz and this property critically relies on the activation of a persistent sodium current, which is counterbalanced by the delayed activation of an A-type potassium current. Furthermore, the interaction between these conductances with the membrane passive properties supports the presence of electrical resonance, whose frequency preference is consistent with both the effective range of hearing in goldfish and the firing frequencies required for synaptic facilitation, an obligatory requisite for the induction of activity-dependent changes. Thus our data show that the presence of a persistent sodium current is functionally essential and allows these afferents to translate behaviorally relevant auditory signals into patterns of activity that match the requirements of their fast and highly modifiable synapses. The functional specializations of these neurons suggest that auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized.
Human Leukocyte Antigen–G and Cancer Immunoediting
Authors: Urosevic Mirjana , Dummer Reinhard
Published: February 2008

Immunosurveillance is an extrinsic mechanism of cancer suppression that eliminates nascent tumors. However, the selection imposed by immunosurveillance can drive tumor evolution and the emergence of clinically apparent neoplasms. Mechanisms of immune escape acquired by less immunogenic variants during this process, termed immunoediting, may contribute significantly to malignant progression. In this review, we summarize the evidence that up-regulation of the nonclassic human leukocyte antigen (HLA) class I molecule HLA-G in tumor cells plays an important role in cancer and immune escape. [Cancer Res 2008;68(3):627–30]
Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer
Authors: Berndt Uta , Philipsen Lars , Bartsch Sebastian , Wiedenmann Bertram , Baumgart Daniel C. , Hämmerle Marcus , Sturm Andreas
Published: February 2008

The immune system is a significant determinant of epithelial tumorigenesis, but its role in colorectal cancer pathogenesis is not well understood. The function of the immune system depends upon the integrity of the protein network environment, and thus, we performed MELC immunofluorescence microscopy focusing on the lamina propria. By analyzing structurally intact tissues from colorectal cancer, ulcerative colitis, and healthy colonic mucosa, we used this unique and novel highly multiplexed robotic-imaging technology, which allows visualizing dozens of proteins simultaneously, and explored the toponome in colorectal cancer mucosa for the first time. We identified 1,930 motifs that distinguish control from colorectal cancer tissue. In colorectal cancer, the number of activated T cells is increased, explained by a lack of bax, caspase-3, and caspase-8. Whereas CD4+CD25+ T cells are decreased and are, other than in ulcerative colitis, not activated, cytotoxic T cells are significantly increased in colorectal cancer. Furthermore, the number of activated human lymphocyte antigen (HLA)-DR+ T-cells is increased in colorectal cancer, pointing to an altered antigen presentation. In colorectal cancer, CD3+CD29+ expression and assembly of the LFA-1 and LFA-3 receptor are differentially changed, indicating a distinct regulation of T-cell adhesion in colorectal cancer. We also identified increased numbers of natural killer and CD44+ cells in the colorectal cancer mucosa and nuclear factor-κB as regulator of apoptosis in these cell populations. High-content proteomic analysis showed that colorectal cancer induces a tremendous modification of protein expression profiles in the lamina propria. Thus, topological proteomic analysis may help to unravel the role of the adaptive immune system in colorectal cancer and aid the development of new antitumor immunotherapy approaches. [Cancer Res 2008;68(3):880–8]
Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene Polymorphisms and Toxicity to Capecitabine in Advanced Colorectal Cancer Patients
Authors: Sharma Rohini , Hoskins Janelle M. , Rivory Laurent P. , Zucknick Manuela , London Rosyln , Liddle Christopher , Clarke Stephen J.
Published: February 2008

Purpose: To evaluate the effect of thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR) genotypes on toxicity in patients treated with capecitabine for advanced colorectal cancer and to determine the effect of these polymorphisms on the pretreatment levels of serum folate and plasma homocysteine.

Experimental Design: Fifty-four patients with a diagnosis of metastatic colorectal cancer were treated with fixed-dose capecitabine. Germ line DNA from patients was genotyped for TYMS TSER, TSER*3G>C, and 3′-untranslated 6 bp insertion/deletion (3′ untranslated region insertion/deletion), and MTHFR c.677C>T and c.1298A>C using PCRs and RFLP. Toxicity was graded by National Cancer Institute Common Toxicity Criteria version 2.0. Response was assessed by Response Evaluation Criteria in Solid Tumors.

Results: MTHFR c.677C>T and c.1298A>C genotypes and diplotypes predicted for grade 2/3 toxicities, whereas the TYMS genotypes had no influence. MTHFR c.677 genotype tended to predict overall survival (P = 0.08). MTHFR c.677 influenced pretreatment homocysteine (P < 0.05) and serum folate levels (P < 0.05). Multivariate analysis suggests that MTHFR c.1298 is an independent predictor of toxicity.

Conclusions: This study suggests that common genetic variation in MTHFR but not TYMS may be useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer. In addition, MTHFR single nucleotide polymorphisms predicted serum folate and plasma homocysteine levels, and, combined, these factors may be important predictors of capecitabine-induced toxicity.
Reduction of Glucose Metabolic Activity Is More Accurate than Change in Size at Predicting Histopathologic Response to Neoadjuvant Therapy in High-Grade Soft-Tissue Sarcomas
Authors: Evilevitch Vladimir , Weber Wolfgang A. , Tap William D. , Allen-Auerbach Martin , Chow Kira , Nelson Scott D. , Eilber Fredrick R. , Eckardt Jeffery J. , Elashoff Robert M. , Phelps Michael E. , Czernin Johannes , Eilber Fritz C.
Published: February 2008

Purpose: Change in tumor size as classified by Response Evaluation Criteria in Solid Tumors poorly correlates with histopathologic response to neoadjuvant therapy in patients with soft-tissue sarcomas. The aim of this study was to prospectively evaluate whether positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) allows for a more accurate evaluation of histopathologic response.

Experimental Design: From January 2005 to January 2007, 42 patients with resectable biopsy-proven high-grade soft-tissue sarcoma underwent a FDG-PET/computed tomography scan before and after neoadjuvant treatment. Relative changes in tumor FDG uptake and size from the baseline to the follow-up scan were calculated, and their accuracy for assessment of histopathologic response was compared by receiver operating characteristic curve analysis. Histopathologic response was defined as ≥95% tumor necrosis.

Results: In histopathologic responders (n = 8; 19%), reduction in tumor FDG uptake was significantly greater than in nonresponders (P < 0.001), whereas no significant differences were found for tumor size (P = 0.24). The area under the receiver operating characteristic curve for metabolic changes was 0.93, but only 0.60 for size changes (P = 0.004). Using a 60% decrease in tumor FDG uptake as a threshold resulted in a sensitivity of 100% and a specificity of 71% for assessment of histopathologic response, whereas Response Evaluation Criteria in Solid Tumors showed a sensitivity of 25% and a specificity of 100%.

Conclusion: Quantitative FDG-PET was significantly more accurate than size-based criteria at assessing histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response in patients with high-grade soft-tissue sarcoma.
Molecular Targeting and Treatment of Composite EGFR and EGFRvIII-Positive Gliomas Using Boronated Monoclonal Antibodies
Authors: Yang Weilian , Wu Gong , Barth Rolf F. , Swindall Michele R. , Bandyopadhyaya Achintya K. , Tjarks Werner , Tordoff Kevin , Moeschberger Melvin , Sferra Thomas J. , Binns Peter J. , Riley Kent J. , Ciesielski Michael J. , Fenstermaker Robert A. , Wikstrand Carol J.
Published: February 2008

Purpose: The purpose of the present study was to evaluate the anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), cetuximab, (IMC-C225) and the anti-EGFRvIII mAb, L8A4, used in combination as delivery agents for boron neutron capture therapy (BNCT) of a rat glioma composed of a mixture of cells expressing either wild-type (F98EGFR) or mutant receptors(F98npEGFRvIII).

Experimental Design: A heavily boronated polyamidoamine dendrimer (BD) was linked by heterobifunctional reagents to produce the boronated mAbs, BD-C225 and BD-L8A4. For in vivo biodistribution and therapy studies, a mixture of tumor cells were implanted intracerebrally into Fischer rats. Biodistribution studies were carried out by administering 125I-labeled bioconjugates via convection-enhanced delivery (CED), and for therapy studies, nonradiolabeled bioconjugates were used for BNCT. This was carried out 14 days after tumor implantation and 24 h after CED at the Massachusetts Institute of Technology nuclear reactor.

Results: Following CED of a mixture of 125I-BD-C225 and 125I-BD-L8A4 to rats bearing composite tumors, 61.4% of the injected dose per gram (ID/g) was localized in the tumor compared with 30.8% ID/g for 125I-BD-L8A4 and 34.7% ID/g for 125I-BD-C225 alone. The corresponding calculated tumor boron values were 24.4 μg/g for rats that received both mAbs, and 12.3 and 13.8 μg/g, respectively, for BD-L8A4 or BD-C225 alone. The mean survival time of animals bearing composite tumors, which received both mAbs, was 55 days (P < 0.0001) compared with 36 days for BD-L8A4 and 38 days for BD-C225 alone, which were not significantly different from irradiated controls.

Conclusions: Both EGFRvIII and wild-type EGFR tumor cell populations must be targeted using a combination of BD-cetuximab and BD-L8A4. Although in vitro C225 recognized both receptors, in vivo it was incapable of delivering the requisite amount of 10B for BNCT of EGFRvIII-expressing gliomas.
EPACT II: Project and Methods
Authors: Juillerat Pascal , Froehlich Florian , Felley Christian , Pittet Valérie , Mottet Christian , Gonvers Jean-Jacques , Michetti Pierre , Vader John-Paul
Published: February 2008

Building on the first European Panel on the Appropriateness of Crohn’s Disease Treatment (EPACT I) which was held in Lausanne at the beginning of March 2004, a new panel will be convened in Switzerland (EPACT II, November to December 2007) to update this work. A combined evidence- and panel-based method (RAND) will be applied to assess the appropriateness of therapy for Crohn’s disease (CD). In preparation for the meeting of experts, reviews of evidence-based literature were prepared for major clinical presentations of CD. During the meeting, an international multidis- ciplinary panel that includes gastroenterologists, surgeons and general practitioners weigh the strength of evidence and apply their clinical experience when assessing the appropriateness of therapy for 569 specific indications (clinical scenarios). This chapter describes in detail the process of updating the literature review and the systematic approach of the RAND Appropriateness Method used during the expert panel meeting.
Maintenance of Medically Induced Remission of Crohn’s Disease
Authors: Gonvers Jean-Jacques , Juillerat Pascal , Mottet Christian , Pittet Valérie , Felley Christian , Vader John-Paul , Michetti Pierre , Froehlich Florian
Published: February 2008

The natural history of Crohn’s disease is characterized by recurring flares alternating with periods of inactive disease and remission. This implies that most patients need to take medication for a large period of their life, mostly for maintenance of remission and, intermittently, additional therapy during a flare. Low-dose systemic corticosteroids are not effective in maintaining remission and should not be used for this indication. There is a trend towards a prolonged time to relapse in patients in remission who are treated with budenoside, a corticosteroid with high topical anti-inflammatory activity and low systemic activity. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn’s disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Only a few studies in small numbers of patients have been published on the use of tacrolimus. There is a lack of convincing evidence of efficacy of mycophenolate mofetil. The use of anti-TNF agents may change the future approach to maintenance therapy for Crohn’s disease. Patients who responded clinically to infliximab, adalimumab and certolizumab have maintained their clinical response when receiving repeat infusions or subcutaneous injections, respectively. In patients refractory to other therapies, infliximab may be effective in maintaining remission.
Otosclerosis and Measles Virus – Association or Causation?
Authors: Niedermeyer H.P. , Arnold W.
Published: February 2008

Otosclerosis is a frequent condition which occurs exclusively in the human temporal bone. This peculiar disease affects mainly Caucasians and Indians and may cause conductive, mixed conductive-sensorineural or occasionally merely sensorineural hearing loss. Morphological investigations of the otosclerotic focus show all three phases of a chronic inflammation with bone resorption, formation of new bone and finally eburnation. Various hypotheses about the cause of inflammation were proposed in the past. Immunological reactivity to collagen, the existence of otosclerosis genes (OTSC 1–5) including mutations of the collagen gene 1A1 and 1A2 or a measles virus (MV) infection were suggested. The existence of the MV proteins and RNA within the otosclerotic tissue has been shown by several authors. However, due to mainly technical problems, no further progress to elucidate the role of the virus could be made. Epidemiological studies revealed a dramatic decrease of measles and related diseases such as the subacute sclerosing panencephalitis since the introduction of MV vaccination programs in USA and Europe. Indeed, some surgeons reported decreasing numbers of stapes surgery and a shift towards elder patients. Our epidemiological survey of all patients hospitalized with otosclerosis in Germany between 1993 and 2004 demonstrates a highly significant decrease in otosclerosis among the population vaccinated against the MV. The strong correlation makes it most plausible that the MV is at least one triggering factor for the development of otosclerosis.
Outcome of Renal Insufficiency Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Chirumamilla Amala P. , Wilson Michael F. , Wilding Gregory E. , Chandrasekhar Rameela , Ashraf Hashmat
Published: February 2008

Renal insufficiency (RI) is a prognostic marker in patients with cardiovascular disease. In this study, the latest standard of glomerular filtration rate (GFR) calculation, that is the modification of diet in renal disease (MDRD) study equation, is used to measure the difference in the outcome of coronary artery bypass graft (CABG) surgery in various GFR groups. Between 2000 and 2005, 1,055 patients underwent CABG surgery and were categorized into 5 groups according to the National Kidney Foundation guidelines: stage 1 = normal renal function; stage 2 = mild RI; stage 3 = moderate RI; stage 4 = severe RI; stage 5 = end-stage renal failure (excluded). Precautions were taken in RI patients to avoid perioperative hypotension, fluid overload and limited cardioplegia; cardiopulmonary bypass time was kept at a minimum by performing an essential number of grafts only. Thirty-day mortality occurred in 5 of 1,052 patients (0.48%) with no statistical difference in stages 1–4. There was increase in bleed requiring reoperation and total complications from stages 1 to 4, but it was not statistically significant. Preoperative renal dysfunction in CABG surgery patients is an important predictor of outcome. Patients undergoing CABG surgery can have acceptable results without significant increase in complications and mortality provided that risk factors are minimized perioperatively.
Incidence of Bleeding in ‘Real-Life’ Acute Coronary Syndrome Patients Treated with Antithrombotic Therapy
Authors: Mortensen Jette , Thygesen Sofie S. , Johnsen Søren P. , Vinther Peter M. , Kristensen Steen D. , Refsgaard Jens
Published: February 2008

Objective: Randomized clinical trials have reported low risks of bleeding in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients receiving triple antithrombotic treatment (aspirin, clopidogrel and heparin). As trial patients often differ substantially from unselected patients treated in routine clinical settings, we compared the incidence of bleeding in ‘real-life patients’ with the incidence in the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial. Methods: We conducted a historical follow-up study based on 195 nonselected patients diagnosed with NSTE-ACS admitted to a Danish hospital. Data were obtained through systematic review of medical records. Bleeding complications were registered for 6 months after the event. Results: One hundred and nineteen (61.0%) patients fulfilled the inclusion and exclusion criteria of the CURE trial and were treated with triple antithrombotic therapy. Eleven (9.2%) of the 119 patients suffered a life-threatening bleeding. Their relative risk of life-threatening bleeding was 4.3 (95% CI 2.4–7.7) compared with the CURE study population. There was no difference in minor bleeding. Among patients not eligible according to the CURE criteria, but receiving intensive antithrombotic treatment, the relative risk of life-threatening bleeding was 6.4 (95% CI 3.1–12.9). Conclusions: When triple antithrombotic therapy is used in clinical practice in NSTE-ACS patients, the risk of bleeding may exceed that reported in trials. Assessment of the bleeding risk in the individual patient is warranted.
Articulatory Variability in Cluttering
Authors: Hartinger Mariam , Mooshammer Christine
Published: February 2008

In order to investigate the articulatory processes of the hasty and mumbled speech in cluttering, the kinematic variability was analysed by means of electromagnetic midsagittal articulography. In contrast to persons with stuttering, those with cluttering improve their intelligibility by concentrating on their speech task. Variability has always been an important criterion in comparable studies of stuttering and is discussed in terms of the stability of the speech motor system. The aim of the current study was to analyse the spatial and temporal variability in the speech of three persons with cluttering (PWC) and three control speakers. All participants were native speakers of German. The speech material consisted of repetitive CV syllables and loan words such as ‘emotionalisieren’, because PWC have the severest problems with long words with a complex syllable structure. The results showed a significantly higher coefficient of variation for PWC in loan word production, both in the temporal and in the spatial domain, whereas the means of displacements and durations did not differ between groups. These findings were discussed in terms of the effects of the linguistic complexity, since for the syllable repetition task, no significant differences between PWC and controls were found.
Kidney Fibrosis in Hypertensive Rats: Role of Oxidative Stress
Authors: Zhao Wenyuan , Chen Sue S. , Chen Yuanjian , Ahokas Robert A. , Sun Yao
Published: February 2008

Fibrosis of the glomerulus and the tubulointerstitium occurs in patients with hypertension. Studies have shown that renal oxidative stress appears in hypertensive kidney disease. The potential role of oxidative stress in renal fibrogenesis remains to be elucidated. Herein, we tested the hypothesis that oxidative stress contributes to the development of renal fibrosis during hypertension.Sprague-Dawley rats received angiotensin II (AngII; 9 µg/h s.c.) for 4 weeks with/without co-treatment of antioxidants, apocynin and tempol (120 mg/kg/day each, p.o.). Untreated rats served as controls. Appearance of renal oxidative stress and its effect on the expression of transforming growth factor (TGF)-β1, population of myofibroblasts, collagen synthesis/degradation and fibrosis in kidneys were examined. Chronic AngII infusion elevated systemic blood pressure (228 ± 6 mm Hg), which was accompanied with extensive renal fibrosis and oxidative stress represented as upregulated NADPH oxidase and suppressed superoxide dismutase (SOD). Co-treatment with antioxidants led to: (1) markedly decreased renal NADPH oxidase; (2) significantly attenuated gene expression of TGF-β1, type I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/-II in the kidney; (3) largely reduced population of myofibroblasts in both the cortex and medulla; (4) significantly reduced renal collagen volume, and (5) partially suppressed blood pressure (190 ± 8 mm Hg). Thus, prolonged AngII administration promotes renal oxidative stress, which is associated with hypertensive renal disease. AngII induces renal oxidative stress by increasing NADPH oxidase and reducing SOD in the kidney, which, in turn, upregulates collagen synthesis, while suppressing collagen degradation, thereby promoting the development of fibrosis in kidneys of hypertensive rats.
Dietary Cholesterol Worsens Adipose Tissue Macrophage Accumulation and Atherosclerosis in Obese LDL Receptor–Deficient Mice
Authors: Subramanian Savitha , Han Chang Yeop , Chiba Tsuyoshi , McMillen Timothy S. , Wang Shari A. , Haw Antonio , Kirk Elizabeth A. , O’Brien Kevin D. , Chait Alan
Published: February 2008

Objective—

Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor–deficient (LDLR
−/−
) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis.

Methods and Results—

LDLR
−/−
mice were fed chow, high-fat, high-carbohydrate (diabetogenic) diets without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers, and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation, and local inflammation were observed in intraabdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group.

Conclusions—

Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation, and increased atherosclerosis in this mouse model.
National US Estimates of Recombinant Tissue Plasminogen Activator Use
Authors: Kleindorfer Dawn , Lindsell Christopher J. , Brass Lawrence , Koroshetz Walter , Broderick Joseph P.
Published: February 2008

Background and Purpose—

Current US estimates of recombinant tissue plasminogen activator (rt-PA) use have been based either on extrapolation of regional studies or on administrative database estimates, both of which may have inherent biases. We sought to compare the utilization of rt-PA in acute ischemic stroke in the MEDPAR database to another national hospital database with drug utilization information.

Methods—

Cases were defined as DRG 14,15, and 524 and ICD-9 code 99.1, which indicates cerebral thrombolysis, for fiscal year 2001 to 2004. Additionally, the Premier database was queried for rt-PA utilization documented in pharmacy records in those patients admitted for stroke. Change over time and difference between databases were tested using Poisson regression.

Results—

When comparing databases, rt-PA use, as identified by ICD-9 code 99.1, was only documented in 0.95% of stroke cases in 2004 in MEDPAR, and 1.2% in the Premier database, which slightly increased by 0.04% to 0.09% over time. Analysis of pharmacy billing records increased the estimate to 1.82%. Exclusion of cases younger than 65years excluded 43% of cases treated with rt-PA. In 2004, 12.7% of cases receiving thrombolytic had either a TIA or a hemorrhagic stroke ICD-9 code.

Conclusions—

We estimate the rate of rt-PA use in the United States to be 1.8% to 2.1% of ischemic stroke patients. The rate of thrombolytic use for ischemic stroke was slightly increasing between 2001 and 2004 at a rate of 0.04% to 0.09% per year. A significant proportion of patients treated with rt-PA are likely miscoded as either TIA or hemorrhagic stroke. We conservatively estimate that 10 800 to 12 600 patients received rt-PA in 2004.
Trends in Incidence and Outcome of Stroke in Perth, Western Australia During 1989 to 2001
Authors: Islam Md. Shaheenul , Anderson Craig S. , Hankey Graeme J. , Hardie Kate , Carter Kristie , Broadhurst Robyn , Jamrozik Konrad
Published: February 2008

Background and Purpose—

We studied temporal trends in major stroke outcomes in Perth, Western Australia (WA), comparing 3 12-month periods, roughly 5 years apart, between 1989 and 2001.

Methods—

The Perth Community Stroke Study (PCSS) used uniform definitions and procedures in a representative segment (approximately 143 000 people in the year 2000) of Perth, WA. Crude and age-standardized incidence and 28-day case fatality for stroke in the different study periods were compared using Poisson regression. We also undertook temporal comparisons of severity, risk factors, and management of stroke to define the basis for any changes in rates. Data are reported with 95% confidence intervals (CI).

Results—

There were 251, 213, and 183 first-ever strokes identified in the first, second, and third study periods, respectively, reflecting significant declines in stroke rates overall, for major age groups, and for both ischemic stroke and intracerebral hemorrhage. The decline in rates was greater in men than women. Compared with the 1989 to 1990 period, sex- and age-adjusted rates declined by 25% (95% CI 10% to 37%) in 1995 to 1996, and by 43% (95% CI 31% to 53%) in 2000 to 2001, corresponding to a 5.5% average annual decrease overall. There were correspondingly significant reductions in the frequencies of key risk factors among cases. However, early case fatality remained stable, both overall and for major pathological subtypes of stroke.

Conclusions—

These data confirm significant declines in the incidence of stroke on the western side of Australia, coincident with some improvement in the vascular risk profile of cases in the population. Decreasing risk rather than improving survival appears to be the main driver of falling mortality from stroke in this population.
Social Support and Stroke and Coronary Heart Disease
Authors: Ikeda Ai , Iso Hiroyasu , Kawachi Ichiro , Yamagishi Kazumasa , Inoue Manami , Tsugane Shoichiro
Published: February 2008

Background and Purpose—

Studies conducted in Western countries have found a robust association between social support and cardiovascular outcomes (eg, prognosis after myocardial infarction and functional recovery after stroke). However, less is known about the influence of social support on the same outcomes among Asian populations. In this prospective cohort study, we sought to examine the impact of social support on the incidence and mortality of coronary heart disease and stroke among the Japanese.

Methods—

We examined prospectively the association between social support and risk of coronary heart disease and stroke incidence and mortality within a cohort of 44 152 Japanese men and women aged 40 to 69 years, free of previous diagnosis of cancer and cardiovascular disease. A total of 301 cases of newly diagnosed coronary heart disease, 1057 strokes, 191 coronary heart disease deaths, and 327 stroke deaths occurred between the baseline questionnaire (1993–1994) and the end of follow-up in January 2004.

Results—

The multivariate hazard ratios and 95% CI for stroke mortality in the highest social support versus lowest social support group was 1.45 (1.00 to 2.10) overall, 1.59 (1.01 to 2.51) for men, and 1.25 (0.63 to 2.46) for women. Social support was not associated with stroke incidence or coronary heart disease incidence and mortality.

Conclusions—

Low social support was associated with higher risk of stroke mortality in men. However, social support was not associated with stroke incidence, suggesting social support may be more important in stroke prognosis than preventing incidence.
Recepción e impacto socio-cognitivo de las noticias sobre inmigración
Authors: Igartua Juan-José , Muñiz Carlos , Otero José , Cheng Lifen , Gómez-Isla José
Published: February 2008

Se ha sugerido que un factor explicativo del rechazo hacia la inmigración es la actuación de los medios de comunicación. Sin embargo, son escasas las investigaciones sobre la recepción e impacto de las noticias sobre inmigración. En este artículo se presenta un estudio experimental sobre los efectos socio-cognitivos de las noticias sobre inmigración. En la investigación participaron 186 estudiantes universitarios. La noticia experimental entregaba información sobre el incremento de la inmigración en España: a) aludiéndose a las consecuencias positivas (contribución económica) o negativas (incremento de la delincuencia); y, b) incluyéndose información sobre el origen de los inmigrantes (latinoamericano versus marroquí). Los resultados mostraron que el tipo de encuadre noticioso enfatizado en la noticia ejercía efectos socio-cognitivos significativos. También se observó un efecto diferencial de la noticia en función del origen de los inmigrantes protagonistas.
Information-Based Skill Scores for Probabilistic Forecasts
Authors: Ahrens Bodo , Walser André
Published: January 2008

The information content, that is, the predictive capability, of a forecast system is often quantified with skill scores. This paper introduces two ranked mutual information skill (RMIS) scores, RMISO and RMISY, for the evaluation of probabilistic forecasts. These scores are based on the concept of mutual information of random variables as developed in information theory. Like the ranked probability skill score (RPSS)—another and often applied skill score—the new scores compare cumulative probabilities for multiple event thresholds. The RMISO quantifies the fraction of information in the observational data that is explained by the forecasts. The RMISY quantifies the amount of useful information in the forecasts. Like the RPSS, the new scores are biased, but they can be debiased with a simple and robust method. This and additional promising characteristics of the scores are discussed with ensemble forecast assessment experiments.
A Diagnostic Case Study of Mei-yu Frontogenesis and Development of Wavelike Frontal Disturbances in the Subtropical Environment
Authors: Chen George Tai-Jen , Wang Chung-Chieh , Chang Sau-Wa
Published: January 2008

During 6–7 June 2003, a mei-yu front over southern China, with active mesoscale convective systems (MCSs) along it and to its south, intensified rapidly in 24 h to possess a strong cyclonic circulation with relative vorticity centers reaching 1.7 × 10−4 s−1 and a low-level jet (LLJ) of 22.5 m s−1 at 850 hPa. Moreover, both the mass and wind fields and convection developed a wavelike structure at meso-α scale along the front. Using mainly gridded analyses from the European Centre for Medium-Range Weather Forecasts (ECMWF), the present study documented the evolution of this case and diagnosed the mechanisms responsible for its rapid intensification and the development of mesoscale disturbances using methods including the piecewise potential vorticity (PV) inversion.

Results indicate that this mei-yu front was characterized by strong horizontal shear and moderate temperature gradient, and its development was not baroclinic in nature. The initiation of a wavelike structure along the frontal shear zone was consistent with barotropic instability. The growth of mesoscale frontal disturbances (cyclogenesis) was a result of the nonlinear mechanism similar to the conditional instability of the second kind (CISK) in which the frontal PV centers and cumulus convection reinforce each other through a positive feedback process.

As the MCSs were both intense and persistent, the latent heating was highly efficient and caused significant enhancement of the mei-yu frontal system, even at latitudes below 25°N. The vorticity budget analysis indicates that the front was maintained mainly by a stretching effect, while its gradual eastward extension and slow southward migration were linked to horizontal advection and a tilting effect, respectively. Induced by the MCSs, the transverse circulation south of the front was exceptionally strong, and the LLJ developed within its lower branch of northward-directed ageostrophic flow through Coriolis torque.
Effects of Terrain Heights and Sizes on Island-Scale Circulations and Rainfall for the Island of Hawaii during HaRP
Authors: Yang Yang , Chen Yi-Leng
Published: January 2008

Islands in Hawaii have different sizes and terrain heights with notable differences in climate and weather. In this study, the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) land surface model (LSM) is used to conduct numerical simulations for the island of Hawaii with different model terrain heights and sizes during the diurnal cycle for the Hawaiian Rainband Project (HaRP) period. In addition to island blocking and orographic lifting, terrain heights also affect the land surface thermal forcing throughout the diurnal cycle by the variations of orographic clouds during the day and by the variations of the longwave radiation heat loss at night. The simulated rainfall distributions and amounts throughout the diurnal cycle are closely related to rising motions caused by nonlinear interactions among island blocking, orographic lifting, and land surface processes. Besides the terrain/mountain height, island size is another factor that affects rainfall production and distribution in Hawaii, because island size affects orographic lifting, surface forcing, and the advection time scale for an air parcel to reach the mountaintop. The heavy rainfall maximum on the mountaintop of the island of Kauai is due to its suitable height and size. This study confirms that the evening rainfall maximum along the western Kona leeside coast is caused by the convergence between the westerly return flow and the offshore flow. For a lower model terrain, the westerly return flow is weaker; as a result, there are smaller evening rainfall amounts.
Quasi-Biweekly Oscillation of the Convection around Sumatra and Low-Level Tropical Circulation in Boreal Spring
Authors: Wen Min , Zhang Renhe
Published: January 2008

The quasi-biweekly oscillation (QBWO) of the tropical convection around Sumatra and its relation to the low-level circulation over the tropical Indian Ocean in boreal spring is investigated. From March to May, the convection over northern Sumatra increases continuously and oscillates with a pronounced period of 10–20 days. Time-lag cross correlations among the QBWOs of the convection, the apparent heat source, and winds in the lower troposphere reveal a possible mechanism of QBWO maintenance. In the strongest phase of the QBWO of the convection around Sumatra, there is an anomalous convective heating symmetric about the equator. The atmospheric Rossby wave response to the heating produces twin cyclones straddling the equator in the west of the convection area. The development of the twin cyclones induces an anomalous southerly north of the equator and a northerly south of the equator at 850 hPa, giving rise to the divergence of the low-level wind field, which weakens the convection around Sumatra. The weakening of the convection leads to the negative phase of convection. In the weakest phase, the Rossby wave response to the anomalous convective cooling produces twin anticyclones symmetric about the equator, resulting in the convergence of the low-level winds and, in turn, enhancing the convection around Sumatra. Consequently, the feedbacks among convection, the Rossby wave response, and the associated wind field at the lower troposphere may be important maintenance mechanisms of the tropical QBWO. The appearance of a tropical westerly is a crucial index of the Asian summer monsoon onset. In the northern equatorial region, the westerly first occurs just to the west of Sumatra, and then extends westward in boreal spring. The westerly around the equator associated with the Rossby wave response to the convective heating of the QBWO of the convection around Sumatra displays a notable intraseasonal feature, which may play an important role in modulating the process of the Asian summer monsoon onset.
Evaluation of a Nonlocal Quasi-Phase Observation Operator in Assimilation of CHAMP Radio Occultation Refractivity with WRF
Authors: Liu Hui , Anderson Jeffrey , Kuo Ying-Hwa , Snyder Chris , Caya Alain
Published: January 2008

A nonlocal quasi-phase radio occultation (RO) observation operator is evaluated in the assimilation of Challenging Minisatellite Payload (CHAMP) radio occultation refractivity using a Weather Research and Forecasting (WRF) ensemble data assimilation system at 50-km resolution. The nonlocal operator calculates the quasi phase through integration of the model refractivity along the observed ray paths. As a comparison, a local refractivity operator that calculates the model refractivity at the observed ray perigee points is also evaluated. The assimilation is done over North America during January 2003 in two different situations: in conjunction with dense, high-quality radiosonde observations and with only satellite cloud drift wind observations. Analyses of temperature and water vapor with the RO refractivity assimilated using the local and nonlocal operator are verified against nearby withheld radiosonde observations. The bias and RMS errors of the analyses of water vapor and temperature using the nonlocal operator are significantly reduced compared with those using the local operator in the troposphere when the only additional observations are satellite cloud drift winds. The reduction of the bias and RMS errors is reduced when radiosonde observations are assimilated.
Numerical Simulations of the Role of Land Surface Conditions in the Evolution and Structure of Summertime Thunderstorms over a Flat Highland
Authors: Yamada Hiroyuki
Published: January 2008

Numerical simulations of summertime thunderstorms over a flat highland (4700 m MSL), assuming the central Tibetan Plateau, were conducted with the use of a cloud-resolving nonhydrostatic model. This study was aimed at clarifying the role of land surface conditions, such as soil moisture and vegetation activity, in the evolution and structure of airmass thunderstorms over the plateau. Two simulations with cyclic lateral boundaries and different surfaces of a dry or wet land were initialized using a unique vertical atmospheric profile at dawn. These initial conditions assume the real atmospheric conditions in two periods of the 1998 summer monsoon, which are characterized by a dry or wet surface. The results of the two experiments were used to examine the contrasting features between the two experiments arising from the different surface conditions. The simulations reproduced differences in the convective structure, the conditions of the subcloud layer, and the evaporation rate of precipitation within this layer. These resulted from different surface-heating processes and were supported by the observational evidence clarified in a previous study. Moreover, the simulations also reproduced the cell broadening occurring in both the boundary and cloud layers and different precipitation processes dependent on the updraft strength. The evidence was partly supported by additional analyses of observational data. This study, therefore, demonstrates a significant effect of the plateau surface upon the cloud evolution and the precipitation process.
Parameterization of Strong Stratospheric Inertia–Gravity Waves Forced by Poleward-Breaking Rossby Waves
Authors: Zülicke Christoph , Peters Dieter
Published: January 2008

The link between poleward-breaking Rossby waves and stratospheric inertia–gravity waves is examined. With a visual inspection of Ertel’s potential vorticity maps based on ECMWF analyses it was found that Rossby wave–breaking events occurred over northern Europe in about 40% of the winter days in 1999–2003. The majority of them were breaking poleward downstream. A total of 10 field campaigns were performed in the winters of 1999–2002 at Kühlungsborn, Germany (54°N, 12°E). They are related to such events and can be considered as representative for poleward-breaking Rossby waves. Inertia–gravity wave properties are diagnosed from radiosonde observations. They appeared to be shallower, slower, and stronger than the climatological mean for the north German lowlands. Hence, Rossby wave–breaking events are linked with strong stratospheric inertia–gravity wave activity. A novel parameterization of inertia–gravity wave generation and propagation is proposed. The stratospheric inertia–gravity wave action in the 16–20-km height range was parameterized with the synoptic-scale cross-stream ageostrophic wind, which accounts for imbalances in the upper-tropospheric jet streak. This empirical relationship is supported with quasigeostrophic theory. Effects of damping and critical level absorption are taken into account with Wentzel–Kramers–Brillouin theory. For verification of the parameterization with homogeneous meteorological fields in space and time, the 10 field campaigns were hindcasted with the nonhydrostatic fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model. About 80% of the variance in inertia–gravity wave action was found to be explained. For the 10 campaigns a close link was found between the poleward-breaking Rossby waves and the strong stratospheric inertia–gravity waves. The role of the polar vortex was twofold: first, it forced the poleward-oriented Rossby waves to break downstream and to form strong tropospheric jet streaks generating inertia–gravity waves. Second, the strong winds in the stratosphere favored the upward propagation of the inertia–gravity waves. The proposed new parameterization of inertia–gravity wave generation and propagation was validated and can be used to deduce mesoscale wave intensity from synoptic flow characteristics during poleward Rossby wave–breaking events.
A Three-Dimensional Anelastic Model Based on the Vorticity Equation
Authors: Jung Joon-Hee , Arakawa Akio
Published: January 2008

A three-dimensional anelastic model has been developed using the vorticity equation, in which the pressure gradient force is eliminated. The prognostic variables of the model dynamics are the horizontal components of vorticity at all heights and the vertical component of vorticity and the horizontally uniform part of the horizontal velocity at a selected height. To implement the anelastic approximation, vertical velocity is diagnostically determined from the predicted horizontal components of vorticity by solving an elliptic equation. This procedure replaces solving the elliptic equation for pressure in anelastic models based on the momentum equation. Discretization of the advection terms uses an upstream-weighted partially third-order scheme. When time is continuous, the solution of this scheme is quadratically bounded. As an application of the model, interactions between convection and its environment with vertical shear are studied without and with model physics from the viewpoint of vorticity dynamics, that is, the deceleration/acceleration process of the basic flow in particular. The authors point out that the process is purely three-dimensional, especially when the convection is relatively localized, involving the twisting terms and the horizontal as well as vertical transports of vorticity. Finally, it is emphasized that parameterization of cumulus friction is a resolution-dependent problem of vorticity dynamics associated with cumulus convection.
Scale-Selective Verification of Rainfall Accumulations from High-Resolution Forecasts of Convective Events
Authors: Roberts Nigel M. , Lean Humphrey W.
Published: January 2008

The development of NWP models with grid spacing down to ∼1 km should produce more realistic forecasts of convective storms. However, greater realism does not necessarily mean more accurate precipitation forecasts. The rapid growth of errors on small scales in conjunction with preexisting errors on larger scales may limit the usefulness of such models. The purpose of this paper is to examine whether improved model resolution alone is able to produce more skillful precipitation forecasts on useful scales, and how the skill varies with spatial scale. A verification method will be described in which skill is determined from a comparison of rainfall forecasts with radar using fractional coverage over different sized areas. The Met Office Unified Model was run with grid spacings of 12, 4, and 1 km for 10 days in which convection occurred during the summers of 2003 and 2004. All forecasts were run from 12-km initial states for a clean comparison. The results show that the 1-km model was the most skillful over all but the smallest scales (approximately <10–15 km). A measure of acceptable skill was defined; this was attained by the 1-km model at scales around 40–70 km, some 10–20 km less than that of the 12-km model. The biggest improvement occurred for heavier, more localized rain, despite it being more difficult to predict. The 4-km model did not improve much on the 12-km model because of the difficulties of representing convection at that resolution, which was accentuated by the spinup from 12-km fields.