bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bibliometric Study of the Use of the Classification and Diagnostic Systems in Psychiatry over the Last 25 Years
Authors: López-Muñoz F. , García-García P. , Sáiz-Ruiz J. , Mezzich J.E. , Rubio G. , Vieta E. , Alamo C.
Published: April 2008

Background: Our purpose was to examine the use of classification and diagnostic systems in the field of psychiatry (CDSP) from a bibliometric perspective, over the period 1980–2005. Methods: We selected (in EMBASE and MEDLINE databases) documents that contained, in any of their sections, the descriptors ‘psychiatr*’, ‘DSM*’, ‘ICD*’, or ‘diagnostic criteria’,as well as other more specific descriptors. As a bibliometric indicator of production we applied Price’s law. We also calculated the national participation index (PI) and correlated it with overall PI in biomedical and health sciences, and with PI in the discipline of psychiatry. Results: We obtained 20,564 original documents; 15,743 referred to the Diagnostic and Statistical Manual of Mental Disorders (DSM) and 3,106 to the International Classification of Diseases (ICD). Our results indicate non-fulfilment of Price’s law, since scientific production on CDSP does not undergo exponential growth (correlation coefficient r = 0.9651, vs. r = 0.9927 after linear adjustment). Of the 10 journals with the highest impact factor in the field of psychiatry, the Journal of Clinical Psychiatry has the highest PI in the DSM subgroup (PI = 14.77), and the British Journal of Psychiatry in the ICD subgroup (PI = 1.54). The principal producer country is the United States (PI = 37.9), though in proportion to its production in the psychiatric field the ranking is headed by Finland. Only 10 countries, of the 20 major producers in health sciences, surpass their own PI in the field of psychiatry (Brazil, Italy, Japan, Austria, Spain, Germany, France, India, Switzerland, and China). Conclusions: Over recent years, the use of CDSP (basically the DSM or ICD) in the scientific literature has increased. Nevertheless, the abstracts to these studies, included in the principal databases, should always specify the diagnostic criteria employed, with a view to increasing information levels and reliability for the reader.
Potential Vulnerability Markers within the Affective Domain in Subjects at Genetic and Clinical High Risk for Schizophrenia
Authors: Lee Seung Jae , Yoo So Young , Kang Do-Hyung , Lee Kyung Jin , Ha Tae Hyun , Wee Whee , Lee Ae-Ra , Kim Nam Sick , Kwon Jun Soo
Published: April 2008

Background: Relative to ample high-risk studies on neurocognitive function, only a few high-risk studies have examined affective functioning components as possible vulnerability markers. In this study, we comprehensively assessed baseline affective functioning in subjects at clinical high risk (CHR) and genetic high risk (GHR) for schizophrenia, and healthy controls (HC), and compared the results to elucidate possible vulnerability markers in the affective domain. Methods: We studied 3 groups of subjects: those with CHR (n = 28) or GHR (n = 28) and a HC group (n = 24). Affective-process- and affective-content-related functioning were assessed using 5 emotion-related scales. Results: In affective process, CHR subjects showed impairments in emotional awareness and mood repair, with some trend of impaired emotional expressivity as well as aggression control relative to either HC or GHR subjects, whereas GHR subjects showed only a trend of impairment in mood repair. In affective content, CHR subjects had less positive and more negative affect scores than the other 2 groups. Conclusions: These results correspond to previous findings of prodrome studies of schizophrenia and chronic schizophrenia and suggest that impaired mood repair and emotional awareness, as well as less positive and more negative affect may be potential candidates of vulnerability markers.
Characterization of Binding Affinity of CJ-023,423 for Human Prostanoid EP4 Receptor
Authors: Murase Akio , Nakao Kazunari , Takada Junji
Published: April 2008

In order to characterize the receptor binding pharmacology of CJ-023,423, a potent and selective EP4 antagonist, we performed a radioligand receptor binding assay under various assay conditions. An acidic (pH 6) and hypotonic buffer is a conventional, well-known buffer for prostaglandin E2 receptor binding assays. CJ-023,423 showed moderate binding affinity for human EP4 receptor under conventional buffer conditions. However, its binding affinity was greatly increased under neutral (pH 7.4) and isotonic buffer conditions. In this report, the binding mechanism between CJ-023,423 and human EP4 receptor is discussed based on the binding affinities determined under various assay conditions.
Skeletal Muscle Morphology and Aerobic Capacity in Patients with Obstructive Sleep Apnoea Syndrome
Authors: Wåhlin Larsson Britta , Kadi Fawzi , Ulfberg Jan , Piehl Aulin Karin
Published: April 2008

Background: Despite the fact that patients with obstructive sleep apnoea syndrome (OSAS) often have symptoms at the level of skeletal muscle such as fatigue, the question of whether the structural, cellular and functional properties of limb skeletal muscles are affected has not been fully examined. Objective: The aim was to examine physiological and muscular parameters in patients with OSAS and to assess the relationship between these parameters and the clinical symptoms. Method: Eighteen patients with OSAS and 16 controls participated. Aerobic capacity was assessed using a submaximal test. Fibre type distribution and fibre area were analyzed on muscle biopsies taken from the tibialis anterior. The microvascularization was assessed using the following parameters: (1) the number of capillaries per fibre (CAF), (2) CAF per fibre area (CAFA), (3) capillary to fibre perimeter exchange (CFPE) index, which represents the interface between muscle fibre and capillaries, and (4) length of capillary/perimeter of the fibre (LC/PF) index or capillary tortuosity, which represents the percent of muscle fibre perimeter in contact with the wall of the microvessel. Results: The OSAS group had significantly lower predicted relative maximal oxygen uptake (p = 0.0047) which was inversely correlated to the apnoea/hypopnoea index (AHI; r = –0.6, p = 0.017). There was a significantly higher CFPE index for slow type I fibres (p = 0.007) and fast type II fibres (p = 0.0126) and a significantly higher LC/PF index for type I fibres (p = 0.0003) and type II fibres (p = 0.0285) in OSAS patients compared to controls. Conclusion: OSAS patients have a higher muscle microvascularization and a lower aerobic capacity than controls. Furthermore the aerobic capacity was inversely correlated to AHI.
Validation of Two Instruments to Assess Technical Bronchoscopic Skill Using Virtual Reality Simulation
Authors: Davoudi Mohsen , Osann Kathryn , Colt Henri G.
Published: April 2008

Background: In an era of increased emphasis on patient safety and competency-based education, demonstration of significant variability in the teaching of flexible bronchoscopy has led to initiatives for new standardized curricula and assessment tools. Objectives: To evaluate the efficacy of such curricula and to assess bronchoscopic skill, 2 measuring instruments have been developed: the Bronchoscopy Skills and Tasks Assessment Tool (BSTAT) and the Bronchoscopy Step-by-Step Evaluation Tool (BSET). We studied the validity and reliability of these 2 instruments. Methods: Two independent testers simultaneously scored 22 volunteer participants at 3 levels [novice (n = 7), fellow (n = 8) and attending (n = 7)] on a virtual reality bronchoscopy simulator using the 2 instruments; each participant was tested twice, in 2 separate sessions. Intertester and test-retest reliability were analyzed with intraclass correlations (ICC); ANOVA was used to assess concurrent validity based on the subjects’ expected skill level. Results: The ICCs between the testers were 0.98 for both the BSTAT and BSET. Comparison of the scores between the sessions showed high test-retest reliability by ICC (0.86 and 0.85 for BSTAT and BSET respectively), with a small yet statistically significant learning effect. The novice group’s scores were lower than the fellows’ and attendings’ (p < 0.001) for both the BSTAT and BSET; the fellows’ scores were consistently lower than the attendings’ on both tests, yet the differences were not statistically significant. Conclusion: This validation study of 2 objective tests of bronchoscopic skill demonstrated high reliability and concurrent validity. These instruments can now be used to evaluate the effectiveness of new competency-based bronchoscopy curricula.
Determinants of Compliance in a Cluster Randomised Controlled Trial on Screening of Breast and Cervix Cancer in Mumbai, India
Authors: Dinshaw Ketayun , Mishra Gauravi , Shastri Surendra , Badwe Rajendra , Kerkar Rajendra , Ramani Subhash , Thakur Meenakshi , Uplap Pallavi , Kakade Anagha , Gupta Subhadra , Ganesh Balasubramanian
Published: April 2008

Objectives: This study aims to investigate the efficacy of screening by low-cost technology in down-staging and reducing mortality due to breast and cervix cancer. Methods: The present trial is a community-based, cluster randomised controlled cohort study on screening for breast and cervix cancers (clinical breast examination and visual inspection of the cervix after application of 4% acetic acid). Univariate and multivariate logistic regression analyses are conducted to identify the predictors of participation in screening. Results: The average compliance is 71.43 and 64.93% for breast and cervix cancer screening, respectively, with the highest compliance in round 1. At the end of 3 screening rounds, 94 and 84% of the eligible women were screened at least once for breast and cervix cancer, respectively. Younger women, women from other than Hindu and Muslim communities, school level-educated women, women belonging to lower-income families, Marathi-speaking women, married women and women who had previously consulted for any breast or gynaecological complaints had higher compliance to participation in screening. Conclusions: Good compliance rates to screening have been demonstrated in the trial, reflecting acceptance of the study by the society, which has implications while translating the trial into a programme.
Determinants of Compliance in a Cluster Randomised Controlled Trial on Screening of Breast and Cervix Cancer in Mumbai, India
Authors: Dinshaw Ketayun , Mishra Gauravi , Shastri Surendra , Badwe Rajendra , Kerkar Rajendra , Ramani Subhash , Thakur Meenakshi , Uplap Pallavi , Kakade Anagha , Gupta Subhadra , Ganesh Balasubramanian
Published: April 2008

Objectives: The study aims to investigate the efficacy of screening by low-cost technology in down-staging and reduction of mortality due to breast and cervix cancer. Methods: The present trial is a community-based, cluster randomised controlled cohort study on screening for breast and cervix cancers (clinical breast examination and visual inspection of the cervix after application of 4% acetic acid). Univariate and multivariate logistic regression analyses are conducted to identify the predictors of compliance to referral among screen-positive women and to treatment among cancer cases. Results: The compliance to diagnostic investigations is 73% among screen-positive women referred for breast cancer and 79% among women referred for cervix cancer. Younger women, women working in service or being self-employed, school level-educated women, mother tongue Marathi, participation in screening in all 3 rounds and women referred as screen positive for cervix cancer had higher compliance to diagnostic investigations. The compliance to treatment completion is higher in women diagnosed with breast cancer, at 95%, compared to 86% for cervix cancers and 81% for cervix pre-cancers. Conclusions: Good compliance rates along with a proper system of referral, further investigations, confirmation of diagnosis and treatment as demonstrated in this trial are crucial for successful screening programmes.
Successful in vivo propagation of factor IX-producing hepatocytes in mice: Potential for cell-based therapy in haemophilia B
Authors: Tatsumi Kohei , Kataoka Miho , Shibata Masaru , Naka Hiroyuki , Shima Midori , Hisanaga Michiyoshi , Kanehiro Hiromichi , Okano Teruo , Nakajima Yoshiyuki , Yoshioka Akira , Ohashi Kazuo , Tateno Chise , Yoshizato Katsutoshi
Published: April 2008

Cell-based therapies using isolated hepatocytes have been proposed to be an attractive application in the treatment of haemophilia B due to the normal production of coagulation factor IX (FIX) in these particular cells. Current cell culture technologies have largely failed to provide adequate isolated hepatocytes, so the present studies were designed to examine a new approach to efficiently proliferate hepatocytes that can retain normal biological function, including the ability to synthesize coagulation factors like FIX. Canine or human primary hepatocytes were transplanted into urokinase-type plasminogen activatorsevere combined immunodeficiency (uPA/SCID) transgenic mice. Both donor hepatocytes from canines and humans were found to progressively proliferate in the recipient mouse livers as evidenced by a sharp increase in the circulating blood levels of species-specific albumin, which was correlated with the production and release of canine and human FIX antigen levels into the plasma. Histological examination confirmed that the transplanted canine and human hepatocytes were able to proliferate and occupy >80% of the host livers. In addition, the transplanted hepatocytes demonstrated strong cytoplasmic staining for human FIX, and the secreted coagulation factor IX was found to be haemostatically competent using specific procoagulant assays. In all, the results from the present study indicated that developments based on this technology could provide sufficient FIX-producing hepatocytes for cell-based therapy for haemophilia B.
Survival of von Willebrand factor released following DDAVP in a type 1 von Willebrand disease cohort: Influence of glycosylation, proteolysis and gene mutations
Authors: Riddell Anne F. , Brown Simon A. , Starke Richard , Mackie Ian , Bowen Derrick J. , Jenkins P. Vincent , van Mourik Jan , Millar Carolyn M.
Published: April 2008

Reduced plasma survival of von Willebrand factor (VWF) may contribute towards the pathogenesis of type 1 von Willebrand disease (VWD). However, little is known about mechanism(s) of VWF clearance and factors that may affect it. The half-life of VWF-related parameters following the administration of DDAVP was measured in 26 patients with type 1 VWD and 10 haemophilia A controls. Binding of lectins Ricinus communis (RCA-I) and Erythina crystagalli (ECA) agglutinins to VWF and VWF susceptibility to ADAMTS-13-mediated proteolysis were investigated. Sequence analysis of targeted regions of the VWF gene was performed to inspect for mutations that have been associated with increased clearance. Post-DDAVP clearance of VWF was increased approximately three-fold in the type 1 VWD cohort overall. However this was not shown to consistently associate with steady-state VWF antigen (VWF:Ag) levels. Furthermore, increased VWF clearance was not consistently associated with increased ratios of VWF propeptide (VWFpp) to VWF:Ag indicating that a normal ratio does not necessarily reflect normal post-DDAVP survival in type 1 VWD patients. RCA-I and ECA binding to VWF were increased in type 1 VWD patients and, although inversely correlated with VWF levels, this was independent of VWF clearance. There was no association between VWF clearance and ADAMTS-13-mediated proteolysis. Three novel candidate mutations with an increased clearance phenotype were identified. The data are consistent with heterogeneity in pathogenic mechanisms in type 1 VWD and are consistent with type 1 VWD representing a complex genetic trait.
Bivalirudin
Authors: Greinacher Andreas , Koster Andreas , Warkentin Theodore
Published: April 2008

Bivalirudin is a direct thrombin inhibitor (DTI) frequently used for anticoagulation in the setting of invasive cardiology, particularly percutaneous coronary intervention (PCI). Bivalirudin has a unique pharmacologic profile: unlike other marketed DTIs, it undergoes predominant non-organ elimination (proteolysis), and has the shortest half-life (~25 min). Its affinity for thrombin is intermediate between that of lepirudin (highest) and argatroban (lowest) — this helps explain why it interferes with functional clotting assays to an extent intermediate between that achieved by these two other DTIs. This effect is best known for the PT (INR) — higher affinity for thrombin corresponds to lower molar DTI requirements to prolong the APTT; in turn, lower concentrations required for APTT prolongation (and, presumably, in-vivo effect) result in reduced PT (INR) prolongation. Bivalirudin is primarily used for its first FDA-approved indication, namely anticoagulation during percutaneous transluminal coronary angioplasty ("balloon angioplasty"), the most frequent type of PCI. Bivalirudin is also indicated for PCI with provisional use of glycoprotein IIb/IIIa antagonist therapy, and for patients with, or at risk of, heparin-induced thrombocytopenia (HIT), or HIT with thrombosis syndrome (HITTS), undergoing PCI. The bivalirudin development program has used a "quadruple" endpoint comprising a "triple" efficacy endpoint plus major bleeding —this approach anticipated the subsequent emphasis on strategies to improve clinical outcomes through bleeding reduction. Besides summarizing the key trials evaluating bivalirudin use for acute coronary syndrome (especially employing PCI), we review also the studies of bivalirudin as anticoagulant for "on-" and "off-pump" cardiac surgery, including both HIT and non-HIT situations.
P-selectin gene haplotypes modulate soluble P-selectin concentrations and contribute to the risk of venous thromboembolism
Authors: Kaider Alexandra , Koder Silvia , Panzer Simon , Pabinger Ingrid , Ay Cihan , Jungbauer Lea , Mannhalter Christine
Published: April 2008

The cell adhesion molecule P-selectin mediates the interaction of activated platelets or endothelial cells with leukocytes. In arterial and venous thromboembolism (VTE) increased soluble P-selectin (sP-selectin) concentrations have been found, and associations of P-selectin genotypes with thrombotic disease have been proposed. We assessed the effect of four single nucleotide polymorphisms (SNPs) [one in the promoter region (c.–2123C>G) and three (S290N, c.1087G>A; D562N, c.1902G>A; T715P, c.2363A>C) in the coding region] and the calculated haplotypes in the P-selectin gene (SELP) on sP-selectin concentrations and VTE risk. The analysis was carried out in 116 high-risk patients with a history of objectively confirmed recurrent VTE and 129 age- and sex-matched healthy individuals. Haplotypes were generated using computer-assisted haplotype reconstruction with Phase 2.1. sP-selectin (μg/l) was measured by ELISA. Frequencies of all four individual SNPs were not statistically significantly different between patients and controls. Tenhaplotypes were obtained for the control population, and nine for the patient group. The most frequent haplotype among controls was CGGA (major allele at all positions) (27.8%; frequency in patients 19.0%), which was used as reference for statistical analyses. Among patients GGAA was most frequent (23.3%; frequency in controls 17.5%). Haplotypes were significantly associated with sP-selectin concentrations in patients and in controls (p<0.001 and p=0.011). Compared to CGGA some but not all haplotypes conferred an increased risk for VTE with odds ratios (ORs) between 5.4 (95% CI: 2.5–12.2) for CAGA, 3.3 (1.2–9.2) for CGAC, and 2.4 (1.3–4.7) for GGAA. All ORs remained statistically significant after adjustment for the factor V Leiden mutation, located in close proximity to SELP on chromosome 1, as well as all other established risk factors for VTE. In conclusion, SELP haplotypes modulate plasma concentrations of sP-selectin and affect the risk of recurrent VTE.
Haematopoietic growth factors and their therapeutic use
Authors: Thorpe Robin , Wadhwa Meenu
Published: April 2008

Haematopoietic growth factors constitute an important group of proteins that predominantly regulate the process of haematopoiesis. While some of these proteins have a very broad array of action on very early haematopoietic progenitors leading to multi-lineage increases in haematopoietic cell production and differentiation, others act in a restricted manner on specific committed terminally differentiated cell types. On the basis of their unique spectrum of activities, several factors are approved for clinical use in various indications while others are under investigation in the clinic either alone or as combination therapy. In this review, we have described factors which directly and in some cases indirectly influence haematopoiesis with particular focus on those factors which are either approved or show potential for clinical use. A brief description of the products that are currently available for clinical use is also provided. At present, several new products which include fusion proteins, peptide mimetics are either at the pre-clinical stage or in clinical development for various indications and these are also briefly described.
Clinical and echocardiographic measures governing thromboembolism destination in atrial fibrillation
Authors: McBane Robert , Hodge David , Wysokinski Waldemar
Published: April 2008

Although infrequent, embolic occlusion to non-cerebral arteries may result in limb loss, organ failure, and death. The aim of this study was to define clinical and echocardiographic characteristics determining thromboembolism destination in non-valvular atrial fibrillation. An inception cohort of individuals (n=72) were identified with incident peripheral embolism in the setting of non-valvular atrial fibrillation (1995–2005). A randomly selected group of atrial fibrillation related stroke patients (n=100) were identified for comparison. Arteries of the extremities were the most common site of embolism (85%); lower extremity involvement was twice as common compared with the upper extremity. Clinical features distinguishing peripheral embolism from stroke included age > 75, heart failure and hypertension. Severe left ventricular dysfunction, spontaneous echo contrast and left atrial thrombus were 2–3 fold more common in peripheral embolism patients. Mean CHADS-2 scores were low and comparable for both groups. By multivariate analysis, age>75 years (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.3–3.9; p=0.05) was predictive of peripheral embolism. After adjustment for age > 75 years, severe left atrial enlargement (HR 1.8, 95% CI 0.99–3.1; p=0.055) and CHADS score (HR 1.2, 95% CI 0.99–1.6; p=0.06) were of borderline significance. In conclusion, several clinical and echocardiographic measures distinguish the clinical presentation of thromboembolism in non-valvular atrial fibrillation. Small emboli are destined to lodge in the cerebral circulation as a result of hydrodynamic, anatomic, and physical factors. Advanced age, atrial enlargement and other comorbidities may increase the propensity for the formation of larger thrombi which may bypass the carotid orifice merely as a function of size.
S100A8 and S100A9 Mediate Endotoxin-Induced Cardiomyocyte Dysfunction via the Receptor for Advanced Glycation End Products
Authors: Boyd John H. , Kan Bernard , Roberts Haley , Wang Yingjin , Walley Keith R.
Published: April 2008

Cardiovascular dysfunction as a result of sepsis is the leading cause of death in the critically ill. Cardiomyocytes respond to infectious pathogens with a Toll-like receptor–initiated proinflammatory response in conjunction with a decrease in contractility, although the downstream events linking Toll-like receptor activation and reduced cardiac contractility remain to be elucidated. Using microarray analysis of cardiac tissue exposed to systemic lipopolysaccharide (LPS), we discovered that 2 small calcium-regulating proteins (S100A8 and S100A9) are highly upregulated. HL-1 cardiomyocytes, isolated primary cardiomyocytes, and live mice were exposed to LPS, whereas beating HL-1 cells had S100A8 and S100A9 overexpressed and their calcium flux quantified. Using in vivo microbubble technology, we delivered S100A8 and S100A9 to normal mouse hearts; using the same technology, we inhibited S100A9 production in mouse hearts and subsequently exposed them to LPS. Coimmunoprecipitation of S100A8 and S100A9 identified interaction with RAGE (the receptor for advanced glycation end products), the cardiac function and postreceptor signaling of which were investigated. HL-1 cardiomyocytes, isolated primary cardiomyocytes, and whole hearts exposed to LPS have large increases in S100A8 and S100A9. Cardiac overexpression of S100A8 and S100A9 led to a RAGE-dependent decrease in calcium flux and, in the intact mouse, to a decreased cardiac ejection fraction, whereas knockdown of S100A9 attenuated LPS-induced cardiac dysfunction. Cardiomyocytes exposed to LPS express S100A8 and S100A9, leading to a RAGE-mediated decrease in cardiomyocyte contractility. This finding provides a novel mechanistic link between circulating pathogen-associated molecular products and subsequent cardiac dysfunction.
Fas System Activation in Perihematomal Areas After Spontaneous Intracerebral Hemorrhage
Authors: Delgado Pilar , Cuadrado Eloy , Rosell Anna , Álvarez-Sabín José , Ortega-Aznar Arantxa , Hernández-Guillamón Mar , Penalba Anna , Molina Carlos A. , Montaner Joan
Published: April 2008

Background and Purpose—

Apoptosis has been implicated as the prominent form of cell death in the brain perihematomal region in animal models and in autopsy or postsurgical human studies. Both the Fas system and caspase activation play a central role in apoptotic pathways. The aims of this study were to investigate soluble Fas (s-Fas) plasma levels after acute intracerebral hemorrhage (ICH), to determine its influence on clinical and radiologic features, and to assess Fas receptor and Fas ligand (Fas-L) protein expression in human ICH brain tissue.

Methods—

s-Fas plasma levels were determined on admission in 78 consecutive ICH patients and serially in a subgroup of 21 of them, at the time of neurologic assessment, by means of ELISA. ICH and perihematomal edema volumes were determined at baseline and on follow-up computed tomography scans, and ICH and perihematomal edema growth was calculated. The presence of Fas receptor and Fas-L was assessed in different brain tissue samples by immunoblotting from 6 deceased ICH patients and from 2 control subjects.

Results—

Mortality reached 20.5% of patients at the third month, and 48% of survivors had an unfavorable outcome (modified Rankin Scale score ≥3). The baseline s-Fas level in ICH patients was significantly lower than in healthy controls [160 (160–245) vs 269 (230–332) pg/mL,
P
<0.001], returning to normal values by 24 hours (
P
<0.05 for all determinations). Regarding radiologic features, the baseline s-Fas value was found to be inversely correlated to perihematomal edema growth at follow-up (
r
=−0.33,
P
=0.041). Finally, Fas-L content was highest in the perihematomal area compared with contralateral and remote ipsilateral areas in ICH patient and control samples.

Conclusions—

A decreased plasma s-Fas level together with an increased Fas-L amount in perihematomal brain tissue suggest Fas-mediated apoptosis involvement in this disease.
Predicting Long-Term Outcome After Acute Ischemic Stroke
Authors: König Inke R. , Ziegler Andreas , Bluhmki Erich , Hacke Werner , Bath Philip M.W. , Sacco Ralph L. , Diener Hans C. , Weimar Christian
Published: April 2008

Background and Purpose—

An early and reliable prognosis for recovery in stroke patients is important for initiation of individual treatment and for informing patients and relatives. We recently developed and validated models for predicting survival and functional independence within 3 months after acute stroke, based on age and the National Institutes of Health Stroke Scale score assessed within 6 hours after stroke. Herein we demonstrate the applicability of our models in an independent sample of patients from controlled clinical trials.

Methods—

The prognostic models were used to predict survival and functional recovery in 5419 patients from the Virtual International Stroke Trials Archive (VISTA). Furthermore, we tried to improve the accuracy by adapting intercepts and estimating new model parameters.

Results—

The original models were able to correctly classify 70.4% (survival) and 72.9% (functional recovery) of patients. Because the prediction was slightly pessimistic for patients in the controlled trials, adapting the intercept improved the accuracy to 74.8% (survival) and 74.0% (functional recovery). Novel estimation of parameters, however, yielded no relevant further improvement.

Conclusions—

For acute ischemic stroke patients included in controlled trials, our easy-to-apply prognostic models based on age and National Institutes of Health Stroke Scale score correctly predicted survival and functional recovery after 3 months. Furthermore, a simple adaptation helps to adjust for a different prognosis and is recommended if a large data set is available.
Meta-Analysis of the Efficacy of Granulocyte-Colony Stimulating Factor in Animal Models of Focal Cerebral Ischemia
Authors: Minnerup Jens , Heidrich Jan , Wellmann Jürgen , Rogalewski Andreas , Schneider Armin , Schäbitz Wolf-Rüdiger
Published: April 2008

Background and Purpose—

Recent reports have described the efficacy of the hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) in animal stroke models. Early clinical multicenter trials evaluating the effect of G-CSF in acute stroke and pilot clinical trials for the subacute phase are ongoing. To guide further development, a meta-analysis was performed to assess the effects of G-CSF on infarct size and sensorimotor deficits.

Methods—

Using electronic and manual searches of the literature, we identified studies describing the efficacy of G-CSF in animal models of focal cerebral ischemia. Two reviewers independently selected studies and extracted data on study quality, G-CSF doses, time of administration, and outcome measured as infarct volume and/or sensorimotor deficit. Data from all studies were pooled by meta-regression analyses.

Results—

Thirteen studies including 277 animals for infarct size calculation and 258 animals for assessment of sensorimotor deficit met the criteria for inclusion. Overall efficacy of G-CSF regarding infarct size reduction was 42%. Meta-regression analysis revealed a 0.8% (
P
<0.0001) decrease in infarct size per 1-μg/kg increase in G-CSF dose when applied within the first 6 hours and a 2.1% (
P
<0.0001) decrease when applied later than 6 hours after induction of ischemia with a significant (
P
=0.0004) greater infarct size reduction after delayed treatment. Sensorimotor deficits categorized into 3 subgroups improved between 24% and 40%.

Conclusions—

Our findings consolidate G-CSF as a drug that both reduces infarct size and enhances functional recovery. These effects are presumably dose dependent. In contrast to most other neuroprotectants, a beneficial outcome may also be achieved when treatment is delayed.
Critical Cap Thickness and Rupture in Symptomatic Carotid Plaques
Authors: Redgrave Jessica N. , Gallagher Patrick , Lovett Joanna K. , Rothwell Peter M.
Published: April 2008

Background and Purpose—

Advances in carotid plaque imaging could allow quantification of fibrous cap thickness in vivo. While a cap thickness <65 μm is the accepted definition of rupture-prone plaque in the coronary circulation, the threshold value for carotid plaques is unknown.

Methods—

We made detailed histological assessments of 526 carotid plaques from consecutive patients undergoing endarterectomy for symptomatic carotid stenosis. The thickness of the fibrous cap at the thinnest and most representative part was measured.

Results—

Cap thickness could be measured reliably in 428 (81%) plaques. In the ruptured plaques (n=257), the median representative cap thickness was 300 μm (IQR 200 to 500 μm) and the median minimum cap thickness was 150 μm (80 to 210 μm; mean=181 μm), which is much greater than the mean cap thickness of 23 μm at the point of rupture that has been reported for coronary plaques. For nonruptured plaques, the median cap thickness values were 500 μm (300 to 700 μm) and 250 μm (180 to 400 μm), respectively. The optimum cut-offs for discriminating between ruptured and nonruptured plaques were a minimum cap thickness <200 μm (OR 5.00, 3.26 to 7.65,
P
<0.001), a representative cap thickness <500 μm (OR 3.38, 2.25 to 5.08,
P
<0.001), or a combination of both (OR 5.11, 3.19 to 8.19,
P
<0.001). Minimum and representative cap thickness were only modestly correlated (r
2
=0.30) and were both independently associated with cap rupture.

Conclusions—

Critical cap thickness is greater in carotid plaques than coronary plaques. Minimum and representative cap thicknesses were both independently associated with cap rupture. A combination of minimum cap thickness <200 μm and a representative cap thickness <500 μm identified ruptured plaques most reliably. Prospective imaging studies are required to establish whether these cut points predict clinical events in patients with asymptomatic carotid stenosis.
Effects of Action Observation on Physical Training After Stroke
Authors: Celnik Pablo , Webster Brian , Glasser Davis M. , Cohen Leonardo G.
Published: April 2008

Background and Purpose—

In healthy humans, observation of another individual performing a motor training task (action observation [AO]) facilitates, in the observer, the effects of physical training (PT) on motor memory formation. It is not known whether this facilitatory process, of potential value for neurorehabilitation, occurs after stroke.

Methods—

Eight chronic stroke patients completed this crossover-randomized investigation. A transcranial magnetic stimulation protocol that tests formation of motor memories was used to determine the effects of PT alone and in combination with AO in 2 different forms: congruent (PT+AO
congruent
) and incongruent (PT+AO
incongruent
) to the practiced task.

Results—

The magnitude of motor memory formation was larger with PT+AO
congruent
than with PT alone or PT+AO
incongruent
. This effect was associated with a differential corticomotor excitability change in the muscles acting as agonist and antagonist of the trained/observed movements.

Conclusions—

These results indicate that congruent AO in association with physical training can enhance the effects of motor training after stroke.
Radiative Transfer Modeling of a Coniferous Canopy Characterized by Airborne Remote Sensing
Authors: Essery Richard , Bunting Peter , Rowlands Aled , Rutter Nick , Hardy Janet , Melloh Rae , Link Tim , Marks Danny , Pomeroy John
Published: April 2008

Solar radiation beneath a forest canopy can have large spatial variations, but this is frequently neglected in radiative transfer models for large-scale applications. To explicitly model spatial variations in subcanopy radiation, maps of canopy structure are required. Aerial photography and airborne laser scanning are used to map tree locations, heights, and crown diameters for a lodgepole pine forest in Colorado as inputs to a spatially explicit radiative transfer model. Statistics of subcanopy radiation simulated by the model are compared with measurements from radiometer arrays, and scaling of spatial statistics with temporal averaging and array size is discussed. Efficient parameterizations for spatial averages and standard deviations of subcanopy radiation are developed using parameters that can be obtained from the model or hemispherical photography.
Transport across 48°N in the Atlantic Ocean
Authors: Lumpkin Rick , Speer Kevin G. , Koltermann K. Peter
Published: April 2008

Transports across 48°N in the Atlantic Ocean are estimated from five repeat World Ocean Circulation Experiment (WOCE) hydrographic lines collected in this region in 1993–2000, from time-varying air–sea heat and freshwater fluxes north of 48°N, and from a synthesis of these two data sources using inverse box model methods.

Results from hydrography and air–sea fluxes treated separately are analogous to recently published transport variation studies and demonstrate the sensitivity of the results to either the choice of reference level and reference velocities for thermal wind calculations or the specific flux dataset chosen. In addition, flux-based calculations do not include the effects of subsurface mixing on overturning and transports of specific water masses. The inverse model approach was used to find unknown depth-independent velocities, interior diapycnal fluxes, and adjustments to air–sea fluxes subject to various constraints on the system. Various model choices were made to focus on annually averaged results, as opposed to instantaneous values during the occupation of the hydrographic lines. The results reflect the constraints and choices made in the construction of the model.

The inverse model solutions show only marginal, not significantly different temporal changes in the net overturning cell strength and heat transport across 48°N. These small changes are similar to seasonally or annually averaged numerical model simulations of overturning. Significant variability is found for deep transports and air–sea flux quantities in density layers. Put another way, if one ignores the details of layer exchanges, the model can be constrained to produce the same net overturning for each repeat line; however, constraining individual layers to have the same transport for each line fails.

Diapycnal fluxes are found to be important in the mean but are relatively constant from one repeat line to the next. Mean air–sea fluxes are modified slightly but are still essentially consistent with either the NCEP data or the National Oceanography Centre, Southampton (NOC) Comprehensive Ocean–Atmosphere Data Set (COADS) within error. Modest reductions in air–sea flux uncertainties would give these constraints a much greater impact. Direct transport estimates over broader regions than the western boundary North Atlantic Current are needed to help resolve circulation structure that is important for variability in net overturning.
The Influence of Air–Sea Roughness, Sea Spray, and Storm Translation Speed on Waves in North Atlantic Storms
Authors: Zhang Weiqing , Perrie William
Published: April 2008

A coupled atmosphere–wave–sea spray model system is used to evaluate the impact of sea spray and wave drag on storm-generated waves, their height variations, and directional wave spectra in relation to the storm location and translation speed. Results suggest that the decrease or increase of significant wave height due to spray and wave drag is most significant in high-wind regions to the right of the storm track. These processes are modulations on the maximum-wave region and tend to occur several hours after the peak wind events, depending on the storm translation velocity. The translation speed of the storm is important. The directional variation between local winds and wind-generated waves within rapidly moving storms that outrun the waves is notably different from that of trapped waves, when the dominant waves’ group velocity approximates the storm translation speed. While wave drag and spray can increase or reduce the magnitudes of wind and significant wave height, their nondirectional formulations allow them to have little apparent effect on the directional wave spectra.
Instabilities of a Baroclinic, Double Diffusive Frontal Zone
Authors: Smyth W. D.
Published: April 2008

The linear theory of double diffusive interleaving is extended to take account of baroclinic effects. This study goes beyond previous studies by including the possibility of modes with nonzero tilt in the alongfront direction, which allows for advection by the baroclinic frontal flow. This requires that the stability equations be solved numerically. The main example is based on observations of interleaving on the lower flank of Meddy Sharon, but a range of parameter values is covered, leading to conclusions that are relevant in a variety of oceanic regimes. The frontal zone is treated as infinitely wide with uniform gradients of temperature, salinity, and alongfront velocity. The stationary, vertically symmetric interleaving mode is shown to have maximum growth rate when its alongfront wavenumber is zero, providing validation for previous studies in which this property was assumed. Besides this, there exist two additional modes of instability: the ageostrophic Eady mode of baroclinic instability and a mode not previously identified. The new mode is oblique (i.e., it tilts in the alongfront direction), vertically asymmetric, and propagating. It is strongly dependent on boundary conditions, and its relevance in the ocean interior is uncertain as a result. Effects of variable diffusivity and buoyancy flux ratio are also considered.
Inertia–Gravity Waves Emitted from Balanced Flow: Observations, Properties, and Consequences
Authors: Williams Paul D. , Haine Thomas W. N. , Read Peter L.
Published: April 2008

This paper describes laboratory observations of inertia–gravity waves emitted from balanced fluid flow. In a rotating two-layer annulus experiment, the wavelength of the inertia–gravity waves is very close to the deformation radius. Their amplitude varies linearly with Rossby number in the range 0.05–0.14, at constant Burger number (or rotational Froude number). This linear scaling challenges the notion, suggested by several dynamical theories, that inertia–gravity waves generated by balanced motion will be exponentially small. It is estimated that the balanced flow leaks roughly 1% of its energy each rotation period into the inertia–gravity waves at the peak of their generation.

The findings of this study imply an inevitable emission of inertia–gravity waves at Rossby numbers similar to those of the large-scale atmospheric and oceanic flow. Extrapolation of the results suggests that inertia–gravity waves might make a significant contribution to the energy budgets of the atmosphere and ocean. In particular, emission of inertia–gravity waves from mesoscale eddies may be an important source of energy for deep interior mixing in the ocean.
Warming and Freshening in the Abyssal Southeastern Indian Ocean*
Authors: Johnson Gregory C. , Purkey Sarah G. , Bullister John L.
Published: April 2008

Warming and freshening of abyssal waters in the eastern Indian Ocean between 1994/95 and 2007 are quantified using data from two closely sampled high-quality occupations of a hydrographic section extending from Antarctica northward to the equator. These changes are limited to abyssal waters in the Princess Elizabeth Trough and the Australian–Antarctic Basin, with little abyssal change evident north of the Southeast Indian Ridge. As in previous studies, significant cooling and freshening is observed in the bottom potential temperature–salinity relations in these two southern basins. In addition, analysis on pressure surfaces shows abyssal warming of about 0.05°C and freshening of about 0.01 Practical Salinity Scale 1978 (PSS-78) in the Princess Elizabeth Trough, and warming of 0.1°C with freshening of about 0.005 in the abyssal Australian–Antarctic Basin. These 12-yr differences are statistically significant from zero at 95% confidence intervals over the bottom few to several hundred decibars of the water column in both deep basins. Both warming and freshening reduce the density of seawater, contributing to the vertical expansion of the water column. The changes below 3000 dbar in these basins suggest local contributions approaching 1 and 4 cm of sea level rise, respectively. Transient tracer data from the 2007 occupation qualitatively suggest that the abyssal waters in the two southern basins exhibiting changes have significant components that have been exposed to the ocean surface within the last few decades, whereas north of the Southeast Indian Ridge, where changes are not found, the component of abyssal waters that have undergone such ventilation is much reduced.
The Effect of Breaking Waves on a Coupled Model of Wind and Ocean Surface Waves. Part II: Growing Seas
Authors: Kukulka Tobias , Hara Tetsu
Published: April 2008

This is the second part of a two-part investigation of a coupled wind and wave model that includes the enhanced form drag of breaking waves. The model is based on the wave energy balance and the conservation of air-side momentum and energy. In Part I, coupled nonlinear advance–delay differential equations were derived, which govern the wave height spectrum, the distribution of breaking waves, and vertical air side profiles of the turbulent stress and wind speed. Numeric solutions were determined for mature seas. Here, numeric solutions for a wide range of wind and wave conditions are obtained, including young, strongly forced wind waves. Furthermore, the “spatial sheltering effect” is introduced so that smaller waves in airflow separation regions of breaking longer waves cannot be forced by the wind. The solutions strongly depend on the wave height curvature spectrum at high wavenumbers (the “threshold saturation level”). As the threshold saturation level is reduced, the effect of breaking waves becomes stronger. For young strongly forced waves (laboratory conditions), breaking waves close to the spectral peak dominate the wind input and previous solutions of a model with only input to breaking waves are recovered. Model results of the normalized roughness length are generally consistent with previous laboratory and field measurements. For field conditions, the wind stress depends sensitively on the wave height spectrum. The spatial sheltering may modify the number of breaking shorter waves, in particular, for younger seas.
Are Tropical Cyclones Less Effectively Formed by Easterly Waves in the Western North Pacific than in the North Atlantic?
Authors: Chen Tsing-Chang , Wang Shih-Yu , Yen Ming-Cheng , Clark Adam J.
Published: April 2008

It has been observed that the percentage of tropical cyclones originating from easterly waves is much higher in the North Atlantic (∼60%) than in the western North Pacific (10%–20%). This disparity between the two ocean basins exists because the majority (71%) of tropical cyclogeneses in the western North Pacific occur in the favorable synoptic environments evolved from monsoon gyres. Because the North Atlantic does not have a monsoon trough similar to the western North Pacific that stimulates monsoon gyre formation, a much larger portion of tropical cyclogeneses than in the western North Pacific are caused directly by easterly waves.

This study also analyzed the percentage of easterly waves that form tropical cyclones in the western North Pacific. By carefully separating easterly waves from the lower-tropospheric disturbances generated by upper-level vortices that originate from the tropical upper-tropospheric trough (TUTT), it is observed that 25% of easterly waves form tropical cyclones in this region. Because TUTT-induced lower-tropospheric disturbances often become embedded in the trade easterlies and resemble easterly waves, they have likely been mistakenly identified as easterly waves. Inclusion of these “false” easterly waves in the “true” easterly wave population would result in an underestimation of the percentage of easterly waves that form tropical cyclones, because the TUTT-induced disturbances rarely stimulate tropical cyclogenesis.

However, an analysis of monsoon gyre formation mechanisms over the western North Pacific reveals that 82% of monsoon gyres develop through a monsoon trough–easterly wave interaction. Thus, it can be inferred that 58% (i.e., 82% × 71%) of tropical cyclones in this region are an indirect result of easterly waves. Including the percentage of tropical cyclones that form directly from easterly waves (∼25%), it is found that tropical cyclones formed directly and indirectly from easterly waves account for over 80% of tropical cyclogeneses in the western North Pacific. This is more than the percentage that has been documented by previous studies in the North Atlantic.