bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaemia in rheumatoid arthritis: can we afford to ignore it?
Authors: Bloxham E , Vagadia V , Scott K , Francis G , Saravanan V , Heycock C , Rynne M , Hamilton J , Kelly C A
Published: June 2011

Introduction

Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications.

Methods

The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded.

Results

Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B12 deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism.

Conclusions

Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.
COMPUTABLE SEMANTICS FOR CTL* ON DISCRETE-TIME AND CONTINUOUS-SPACE DYNAMIC SYSTEMS
Authors: COLLINS PIETER , ZAPREEV IVAN S.
Published: June 2011

In this work, we consider Discrete-Time Continuous-Space Dynamic Systems for which we study the computability of the standard semantics of CTL* (CTL, LTL) and provide a variant thereof computable in the sense of Type-2 Theory of Effectivity. In particular, we show how the computable model checking of existentially and universally quantified path formulae of LTL can be reduced to solving, respectively, repeated reachability and persistence problems on a model obtained as a parallel composition of the original one and a non-deterministic Büchi automaton corresponding to the verified LTL formula.
FORMALISMS FOR SPECIFYING MARKOVIAN POPULATION MODELS
Authors: HENZINGER THOMAS , JOBSTMANN BARBARA , WOLF VERENA
Published: June 2011

In this survey, we compare several languages for specifying Markovian population models such as queuing networks and chemical reaction networks. All these languages — matrix descriptions, stochastic Petri nets, stoichiometric equations, stochastic process algebras, and guarded command models — describe continuous-time Markov chains, but they differ according to important properties, such as compositionality, expressiveness and succinctness, executability, and ease of use. Moreover, they provide different support for checking the well-formedness of a model and for analyzing a model.
GENERAL ALGORITHMS FOR TESTING THE AMBIGUITY OF FINITE AUTOMATA AND THE DOUBLE-TAPE AMBIGUITY OF FINITE-STATE TRANSDUCERS
Authors: ALLAUZEN CYRIL , MOHRI MEHRYAR , RASTOGI ASHISH
Published: June 2011

We present efficient algorithms for testing the finite, polynomial, and exponential ambiguity of finite automata with ε-transitions. We give an algorithm for testing the exponential ambiguity of an automaton A in time [Formula: see text], and finite or polynomial ambiguity in time [Formula: see text], where |A|E denotes the number of transitions of A. These complexities significantly improve over the previous best complexities given for the same problem. Furthermore, the algorithms presented are simple and based on a general algorithm for the composition or intersection of automata. Additionally, we give an algorithm to determine in time [Formula: see text] the degree of polynomial ambiguity of a polynomially ambiguous automaton A and present an application of our algorithms to an approximate computation of the entropy of a probabilistic automaton.

We also study the double-tape ambiguity of finite-state transducers. We show that the general problem is undecidable and that it is NP-hard for acyclic transducers. We present a specific analysis of the double-tape ambiguity of transducers with bounded delay. In particular, we give a characterization of double-tape ambiguity for synchronized transducers with zero delay that can be tested in quadratic time and give an algorithm for testing the double-tape ambiguity of transducers with bounded delay.
MEASURING THE QUALITY OF SURVEILLANCE IN A WIRELESS SENSOR NETWORK
Authors: MONDAL DEBASHIS , KUMAR ABHAY , BISHNU ARIJIT , MUKHOPADHYAYA KRISHNENDU , NANDY SUBHAS C.
Published: June 2011

Quality of Surveillance (QoSv) is a generic measure of the coverage offered by a given network of sensors over the field it monitors. In this work, we consider it to be the length of the longest straight line segment that does not pass through the sensing zone of any sensor. It can be seen as the longest length that an intruder may travel along a straight line, before being detected. An easy to implement algorithm for computing the QoSv in a rectangular field [Formula: see text] containing a set of n identical sensors is proposed. The time and space complexities of our algorithm are O(n2 log n) and O(n) respectively. It is also shown that a minor modification of the algorithm runs in O(n2) time and space.
The Role of a Strong Corporate Mission for Knowledge Management
Authors: Magnier-Watanabe Rémy , Senoo Dai
Published: June 2011

This research, using large questionnaire data collected from a Japanese pharmaceutical company, attempts to examine the impact of organisational culture, leadership, and reporting styles on knowledge management, which can support innovation, assessing the significance of levels of comprehension and implementation of the corporate mission. Those with a better understanding and consistent realisation of the corporate mission were found to spend significantly more time on knowledge management activities, suggesting that the organisation should better communicate the corporate mission to employees and translate it into clear objectives.

Moreover, these results have revealed discriminate enablers of knowledge management among employees with higher levels of comprehension and implementation of the corporate mission and those with lower levels. In the former group, time spent on knowledge management activities was solely the result of organisational culture, while in the latter, involvement in knowledge management was the product of both high open-mindedness and more inclusive reporting. These findings suggest first that a strong mission shared and put into practice among the workforce is a powerful driver of knowledge management, and second, that open-mindedness and more inclusive reporting can substitute for a strong corporate mission and support knowledge management activities.
The Dynamics of Growth within Global Organisations: Issues, Consequences and Implications
Authors: Sandhawalia Birinder Singh , Dalcher Darren
Published: June 2011

An ever-accelerating rate of growth is altering the pace of change and making global organisations perform trade-offs in terms of organisational capabilities and quality of output. This paper reports on the empirical findings of a case study conducted at one of the world's largest software organisations and analyses the implications of rapid growth within global organisations. The paper further correlates the findings with the problems and issues confronting the world's largest automobile manufacturer, and establishes that growth needs to be planned to allow organisational capabilities and systems to support rapid expansion. Overall, the research highlights the important lessons learnt from accelerated growth within global organisations, and identifies the areas of future research required to gain a better understanding of the phenomenon.
The role of dystroglycan in PDGF-BB-dependent migration of activated hepatic stellate cells/myofibroblasts
Authors: Kastanis George John , Hernandez-Nazara Zamira , Nieto Natalia , Rincón-Sanchez Ana Rosa , Popratiloff Anastas , Dominguez-Rosales Jose Alfredo , Lechuga Carmen G. , Rojkind Marcos
Published: June 2011

Hepatic stellate cells are embedded in the loose connective tissue matrix within the space of Disse. This extracellular matrix contains several basement membrane components including laminin, but its composition changes during liver injury because of the production of extracellular matrix components found in scar tissue. These changes in extracellular matrix composition and in cell-extracellular matrix interactions may play a key role in hepatic stellate cell transdifferentiation. In this communication we used early passages of mouse hepatic stellate cells (activated HSC/myofibroblasts) to study the platelet-derived growth factor BB (PDGF-BB)-dependent expression and regulation of β-dystroglycan and its role in activated HSC/myofibroblast migration. We used Northern and Western analysis to study dystroglycan expression and confocal microscopy to investigate changes in subcellular distribution of the protein. Activated HSC migration was investigated using an in vitro wound-healing assay. PDGF-BB induced significant changes in dystroglycan regulation and subcellular distribution of the protein. Whereas steady-state levels of dystroglycan mRNA remained constant, PDGF-BB increased dystroglycan transcription but shortened the t1/2by 50%. Moreover, PDGF-BB changed dystroglycan and α5-integrin cellular distribution. Cell migration experiments revealed that PDGF-BB-dependent migration of activated HSC/myofibroblasts was completely blocked by neutralizing antibodies to fibronectin, α5-integrin, laminin, and β-dystroglycan. Overall, these findings suggest that both laminin and fibronectin and their receptors play a key role in PDGF-BB-induced activated HSC migration.
Is sprint exercise a leptin signaling mimetic in human skeletal muscle?
Authors: Guerra Borja , Olmedillas Hugo , Guadalupe-Grau Amelia , Ponce-González Jesús G. , Morales-Alamo David , Fuentes Teresa , Chapinal Esther , Fernández-Pérez Leandro , De Pablos-Velasco Pedro , Santana Alfredo , Calbet Jose A. L.
Published: June 2011

This study was designed to determine whether sprint exercise activates signaling cascades linked to leptin actions in human skeletal muscle and how this pattern of activation may be interfered by glucose ingestion. Muscle biopsies were obtained in 15 young healthy men in response to a 30-s sprint exercise (Wingate test) randomly distributed into two groups: the fasting ( n = 7, C) and the glucose group ( n = 8, G), who ingested 75 g of glucose 1 h before the Wingate test. Exercise elicited different patterns of JAK2, STAT3, STAT5, ERK1/2, p38 MAPK phosphorylation, and SOCS3 protein expression during the recovery period after glucose ingestion. Thirty minutes after the control sprint, STAT3 and ERK1/2 phosphorylation levels were augmented (both, P < 0.05). SOCS3 protein expression was increased 120 min after the control sprint but PTP1B protein expression was unaffected. Thirty and 120 min after the control sprint, STAT5 phosphorylation was augmented ( P < 0.05). Glucose abolished the 30 min STAT3 and ERK1/2 phosphorylation and the 120 min SOCS3 protein expression increase while retarding the STAT5 phosphorylation response to sprint. Activation of these signaling cascades occurred despite a reduction of circulating leptin concentration after the sprint. Basal JAK2 and p38 MAPK phosphorylation levels were reduced and increased (both P < 0.05), respectively, by glucose ingestion prior to exercise. During recovery, JAK2 phosphorylation was unchanged and p38 MAPK phosphorylation was transiently reduced when the exercise was preceded by glucose ingestion. In conclusion, sprint exercise performed under fasting conditions is a leptin signaling mimetic in human skeletal muscle.
A New Microarray System to Detect Streptococcus pneumoniae Serotypes
Authors: Tomita Yuka , Okamoto Akira , Yamada Keiko , Yagi Testuya , Hasegawa Yoshinori , Ohta Michio
Published: June 2011

Streptococcus pneumoniae, one of the most common gram‐positive pathogens to colonize the human upper respiratory tract, is responsible for many severe infections, including meningitis and bacteremia. A 23‐valent pneumococcal vaccine is available to protect against the 23 S. pneumoniae serotypes responsible for 90% of reported bacteremic infections. Unfortunately, current S. pneumoniae serotype testing requires a large panel of expensive antisera, assay results may be subjective, and serotype cross‐reactions are common. For this study, we designed an oligonucleotide‐based DNA microarray to identify glycosyltransferase gene sequences specific to each vaccine‐related serotype. Out of 56 isolates representing different serotypes, only one isolate, representing serotype 23A, was not detected correctly as it could not be distinguished from serotype 23F. Our data suggest that the microarray provides a more cost‐effective and reliable way of monitoring pneumococcal capsular types.
Part‐Metric and Its Applications to Cyclic Discrete Dynamic Systems
Authors: Liu Wanping , Yang Xiaofan , Stević Stevo , Iričanin Bratislav
Published: June 2011

We adapt the part metric and use it in studying positive solutions
of a certain family of discrete dynamic systems. Some examples are presented,
and we also compare some results in the literature.
Sustainability of Teachers' International Experiences: Conditions for Institutionalization of International Program Outcomes
Authors: Rapoport Anatoli
Published: June 2011

Since World War II international exchange and training programs for educators have increasingly played an important role in developing prospective consciousness and awareness of cultural diversity and global interdependence among teachers. However, international programs have always depended on extra educational factors such as political, ideological, cultural, or financial circumstances. As a result, program sustainability and proper institutionalization of program's results that are a testimony of achieved success, are both matters of concern for program developers and alumni. This paper identifies factors and contexts that facilitate sustainable development of international programs and institutionalization of their outcomes. Two cohorts of international teacher program alumni from Russia and the United States were interviewed about the impact of exchange programs on participants' status and pedagogies. The study demonstrated that respondents consider three factors, namely, motivational, administrative, and cooperative, most critical for the institutionalization of international program results.
Aerobic Exercise Training Adaptations Are Increased by Postexercise Carbohydrate-Protein Supplementation
Authors: Ferguson-Stegall Lisa , McCleave Erin , Ding Zhenping , Doerner III Phillip G. , Liu Yang , Wang Bei , Healy Marin , Kleinert Maximilian , Dessard Benjamin , Lassiter David G. , Kammer Lynne , Ivy John L.
Published: June 2011

Carbohydrate-protein supplementation has been found to increase the rate of training adaptation when provided postresistance exercise. The present study compared the effects of a carbohydrate and protein supplement in the form of chocolate milk (CM), isocaloric carbohydrate (CHO), and placebo on training adaptations occurring over 4.5 weeks of aerobic exercise training. Thirty-two untrained subjects cycled 60 min/d, 5 d/wk for 4.5 wks at 75–80% of maximal oxygen consumption (VO2max). Supplements were ingested immediately and 1 h after each exercise session. VO2max and body composition were assessed before the start and end of training. VO2max improvements were significantly greater in CM than CHO and placebo. Greater improvements in body composition, represented by a calculated lean and fat mass differential for whole body and trunk, were found in the CM group compared to CHO. We conclude supplementing with CM postexercise improves aerobic power and body composition more effectively than CHO alone.
The Influence of Controller Parameters on the Quality of the Train Converter Current
Authors: Brenna M. , Foiadelli F. , Zaninelli D.
Published: June 2011

This paper presents a stability analysis of train converters in order to evaluate how the controller parameters affect the absorbed current. The new dynamic model presented in this paper is capable of considering the time-variant nature of the system for the correct tuning of the feedback proportional-integral PI controller, applying a current controlled modulation technique never used in high-power traction converters. The reduction of the harmonic content of the current absorbed by a converter employed at the input stage onboard high-speed trains is really important, considering the interaction with the signaling system set up for traffic control. A computer model of the converter, considering both the power and the control structure, has also been implemented in order to deliver a validated tool for the developed theoretical analysis.
Copper-Metalized GaAs pHEMT with Cu/Ge Ohmic Contacts
Authors: Anichenko E. V. , Arykov V. S. , Erofeev E. V. , Kagadei V. A.
Published: June 2011

The fully Cu-metalized GaAs pHEMT using developed Cu/Ge-based ohmic contacts and T-gate Ti/Mo/Cu with length of the 150 nm has been successfully fabricated for the high-frequency applications. The fabricated Cu-metalized pHEMT has a maximum drain current of 360 mA/mm, an off-state gate-drain breakdown of 7 V, and a transconductance peak of 320 mS/mm at Vds=3 V. The maximum stable gain value was about 15 dB at frequency 10 GHz. The current gain cutoff frequency of the copper-metalized device is about 60 GHz at Vds=3 V, and maximum frequency of oscillations is beyond 100 GHz. This work investigated in detail the formation of Cu/Ge ohmic contacts to n-GaAs with an atomic hydrogen preannealing step. It was shown that after the first preliminary annealing is carried out in a flow of atomic hydrogen with a flow density of atoms of 1013/1016 at. cm2 s−1 a reduction in specific contact resistance by 2/2.5 times is observed. The reduction in specific contact resistance is apparently caused by the action of the hydrogen atoms which minimise the rate of the oxidizing reactions and activate solid phase reactions forming the ohmic contact during the thermal treatment process.
Predictors of Clinical Outcomes of Flexible Ureterorenoscopy with Holmium Laser for Renal Stone Greater than 2 cm
Authors: Al-Qahtani Saeed M. , Gil-deiz-de-Medina Sixtina , Traxer Olivier
Published: June 2011

Objective. To evaluate the clinical outcome of flexible ureterorenoscopy (F-URS) with holmium laser in managing renal stone greater than 2 cm.Patients and Methods. Records of 120 patients (123 renal units) with renal stone greater than 2 cm who underwent F-URS with holmium laser iwere evaluated. The mean stone size was 26.3 mm. Patient and stone characteristics, perioperative outcomes and complications were evaluated. The outcome was determined at 4 weeks on plain radiograph (KUB) and Non-contrast CT scan (NCCT). Follow-up visit was up to 6 months to evaluate the clinical outcome and patients symptoms.Results. Stone burden was an independent predictor of FURS results. After first session of treatment, success rate was obtained in 72 renal units (58.5%). On the other hand, significant residual fragment was encountered in 51 renal units (41.5%). This was improved with “staged-therapy” to 87% and 96.7% after second and third session of treatment, respectively. Complications were recorded. They were managed in proper manner accordingly.Conclusion. This is an attractive, safe and effective technique. It is an ideal option for low volume complex stone with average burdens of 2 to 3 cm. Patient should be informed and consented about staged-therapy.
Prognostic Immune Markers in Non–Small Cell Lung Cancer
Authors: Suzuki Kei , Kachala Stefan S. , Kadota Kyuichi , Shen Ronglai , Mo Qianxing , Beer David G. , Rusch Valerie W. , Travis William D. , Adusumilli Prasad S.
Published: June 2011

Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non–small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients. To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC. Clin Cancer Res; 17(16); 5247–56. ©2011 AACR.
Stereological Assessment of Renal Development in a Baboon Model of Preterm Birth
Authors: Sutherland Megan R. , Gubhaju Lina , Black M. Jane
Published: June 2011

At the time when most preterm babies are delivered, nephrogenesis is still ongoing, with the majority of nephrons normally formed during the third trimester of pregnancy. The extrauterine environment, however, is suboptimal for organogenesis, and therefore renal development is likely to be adversely affected by preterm birth. In the long-term, there is emerging evidence of high blood pressure and renal dysfunction amongst young adults born preterm. There is little knowledge to date, however, regarding the effects of preterm birth on renal structural development, perhaps due to the lack of an appropriate animal model. We have demonstrated that the baboon (Papio sp.) has a similar time course of nephrogenesis as the human kidney, and the baboon neonate can also be cared for in the same manner as a human neonate following preterm birth. Through a series of studies assessing renal development in the baboon model of preterm birth, involving the use of gold-standard stereological techniques, we have demonstrated that nephron endowment in the preterm baboon kidney is not reduced. Furthermore, antenatal glucocorticoid exposure prior to preterm delivery was associated with an increase in mature nephrons. There was, however, evidence of morphological abnormalities in a variable percentage of the glomeruli formed ex utero. Further research is therefore essential in order to establish what factors are involved in contributing to the glomerular abnormalities, and to identify ways in which ‘normal’ renal development can be conserved and optimised in the extrauterine setting.
Resting Blood Pressure Values of Adult Athletes
Authors: Varga-Pintér Barbara , Horváth Patrícia , Kneffel Zsuzsanna , Major Zsuzsanna , Osváth Péter , Pavlik Gábor
Published: June 2011

Background: Regular physical activity has a favorable effect upon the prevention and treatment of hypertension. Various movements in sports, however, affect blood pressure (BP) differently. Methods: In the present study, the resting BP data of a large number (3,697) of young men and women (age: 19–40 years) who participated in sports medical examinations were compared according to their sport. Athletes were arranged into definite subgroups based on their different sport activities, i.e. if their movement pattern characteristics were similar and no significant intergroup differences were seen in BP values. Results: BP values were lower in the dynamic type athletes (speed, endurance sports and ball games) than in the static type. Out of the endurance athletes, BP values were not lower in cycle racers, kayakers/canoeists and rowers. In water athletes, BP values were higher than in corresponding dry-land athletes. There was a quite large significant difference between the BP values of athletes involved in static muscular activity (power athletes) and dynamic-type strength athletes (combat competitors). Conclusions: Although cycling, kayaking/canoeing and competitive water sports increase BP, as leisure time activities they more than likely do not elevate BP.
Oxidative Stress and Endothelin-1 in Atherosclerotic Renal Artery Stenosis and Effects of Renal Angioplasty
Authors: Saeed A. , Herlitz H. , Nowakowska-Fortuna E. , Nilsson U. , Alhadad A. , Jensen G. , Mattiasson I. , Lindblad B. , Gottsäter A. , Guron G.
Published: June 2011

Aims: To examine biomarkers of oxidative stress (oxs), and endothelin (ET)-1, in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) and to evaluate the effect of percutaneous transluminal renal angioplasty (PTRA). Methods: Baseline measurements were made immediately before renal angiography in patients with suspected ARAS (significant ARAS, n = 83, and non-RAS, n = 59) and in 20 healthy, matched controls. In patients with ARAS, analyses were repeated 4 weeks after PTRA. All patients were treated with statins and acetylsalicylic acid throughout. Results: At baseline there were no significant differences between groups in biomarkers of oxs, whereas high-sensitivity C-reactive protein and blood leukocytes were significantly elevated in group ARAS versus both healthy controls and group non-RAS. Plasma levels of ET-1 and uric acid were significantly increased in group ARAS versus healthy controls prior to angiography and were significantly reduced compared to baseline 4 weeks after PTRA. PTRA had no significant effects on biomarkers of oxs, inflammation or serum creatinine concentrations. Conclusions: ARAS patients on treatment with antihypertensive agents, acetylsalicylic acid and statins showed elevated inflammatory indices but no increase in oxs. PTRA had no significant effects on inflammatory indices 4 weeks after intervention but reduced plasma ET-1 and uric acid.
Malignancies Confined to Disused Arteriovenous Fistulae in Renal Transplant Patients: An Important Differential Diagnosis
Authors: Webster Philip , Wujanto Lareina , Fisher Cyril , Walker Marjorie , Ramakrishnan Rathi , Naresh Kikkeri , Thomas J. Meirion , Papalois Vassilios , Crane Jeremy , Taube David , Duncan Neill
Published: June 2011

Background: Swelling in an arteriovenous fistula (AVF) is commonly caused by thrombosis, aneurysm and infection. However, due to the increased risk of malignancy after transplantation, this should also be considered. Patients: We discuss 4 patients with malignancy confined to an AVF after renal transplantation presenting in a 2-year period. Angiosarcoma was diagnosed in 3 patients and the other had post-transplant lymphoproliferative disorder (PTLD). Angiosarcoma behaves aggressively and 2 of our patients died within 6 months of diagnosis. There are 6 previous cases and 5 died within 16 months of diagnosis. PTLD at AVFs has not been documented previously. Conclusion: Malignancy at an AVF is a rare but important differential that can impact significantly on patient morbidity and mortality. Predilection for malignancy at an AVF is not understood. We review the literature and discuss possible aetiologies.
Cdc42 Controls Vascular Network Assembly Through Protein Kinase Cι During Embryonic Vasculogenesis
Authors: Qi Yanmei , Liu Jie , Wu Xunwei , Brakebusch Cord , Leitges Michael , Han Yaling , Corbett Siobhan A. , Lowry Stephen F. , Graham Alan M. , Li Shaohua
Published: June 2011

Objective—

The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms.

Methods and Results—

By using genetically modified mouse embryonic stem (ES) cells, we demonstrate that ablation of the Rho GTPase Cdc42 blocks vascular network assembly during embryoid body (EB) vasculogenesis without affecting endothelial lineage differentiation. Reexpression of Cdc42 in mutant EBs rescues the mutant phenotype, establishing an essential role for Cdc42 in vasculogenesis. Chimeric analysis revealed that the vascular phenotype is caused by inactivation of Cdc42 in endothelial cells rather than surrounding cells. Endothelial cells isolated from Cdc42-null EBs are defective in directional migration and network assembly. In addition, activation of atypical protein kinase Cι (PKCι) is abolished in Cdc42-null endothelial cells, and PKCι ablation phenocopies the vascular abnormalities of the Cdc42-null EBs. Moreover, the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 depends on Cdc42 and PKCι, and expression of kinase-dead GSK-3β in Cdc42-null EBs promotes the formation of linear endothelial segments without branches. These results suggest that PKCι and GSK-3β are downstream effectors of Cdc42 during vascular morphogenesis.

Conclusion—

Cdc42 controls vascular network assembly but not endothelial lineage differentiation by activating PKCι during embryonic vasculogenesis.
Quantification of Monthly Mean Regional-Scale Albedo of Marine Stratiform Clouds in Satellite Observations and GCMs
Authors: Bender Frida A.-M. , Charlson Robert J. , Ekman Annica M. L. , Leahy Louise V.
Published: June 2011

Planetary albedo—the reflectivity for solar radiation—is of singular importance in determining the amount of solar energy taken in by the Earth–atmosphere system. Modeling albedo, and specifically cloud albedo, correctly is crucial for realistic climate simulations. A method is presented herein by which regional cloud albedo can be quantified from the relation between total albedo and cloud fraction, which in observations is found to be approximately linear on a monthly mean scale. This analysis is based primarily on the combination of cloud fraction data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and albedo data from the Clouds and the Earth’s Radiant Energy System (CERES), but the results presented are also supported by the combination of cloud fraction and proxy albedo data from satelliteborne lidar [Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO)]. These data are measured and derived completely independently from the CERES–MODIS data. Applied to low-level marine stratiform clouds in three regions (off the coasts of South America, Africa, and North America), the analysis reveals regionally uniform monthly mean cloud albedos, indicating that the variation in cloud shortwave radiative properties is small on this scale. A coherent picture of low “effective” cloud albedo emerges, in the range from 0.35 to 0.42, on the basis of data from CERES and MODIS. In its simplicity, the method presented appears to be useful as a diagnostic tool and as a constraint on climate models. To demonstrate this, the same method is applied to cloud fraction and albedo output from several current-generation climate models [from the Coupled Model Intercomparison Project, phase 3 (CMIP3), archive]. Although the multimodel mean cloud albedo estimates agree to within 20% with the satellite-based estimates for the three focus regions, model-based estimates of cloud albedo are found to display much larger variability than do the observations, within individual models as well as between models.
Ice Crystals Growing from Vapor in Supercooled Clouds between −2.5° and −22°C: Testing Current Parameterization Methods Using Laboratory Data
Authors: Westbrook C. D. , Heymsfield A. J.
Published: June 2011

The physical and empirical relationships used by microphysics schemes to control the rate at which vapor is transferred to ice crystals growing in supercooled clouds are compared with laboratory data to evaluate the realism of various model formulations.

Ice crystal growth rates predicted from capacitance theory are compared with measurements from three independent laboratory studies. When the growth is diffusion- limited, the predicted growth rates are consistent with the measured values to within about 20% in 14 of the experiments analyzed, over the temperature range −2.5° to −22°C. Only two experiments showed significant disagreement with theory (growth rate overestimated by about 30%–40% at −3.7° and −10.6°C).

Growth predictions using various ventilation factor parameterizations were also calculated and compared with supercooled wind tunnel data. It was found that neither of the standard parameterizations used for ventilation adequately described both needle and dendrite growth; however, by choosing habit-specific ventilation factors from previous numerical work it was possible to match the experimental data in both regimes.

The relationships between crystal mass, capacitance, and fall velocity were investigated based on the laboratory data. It was found that for a given crystal size the capacitance was significantly overestimated by two of the microphysics schemes considered here, yet for a given crystal mass the growth rate was underestimated by those same schemes because of unrealistic mass/size assumptions. The fall speed for a given capacitance (controlling the residence time of a crystal in the supercooled layer relative to its effectiveness as a vapor sink, and the relative importance of ventilation effects) was found to be overpredicted by all the schemes in which fallout is permitted, implying that the modeled crystals reside for too short a time within the cloud layer and that the parameterized ventilation effect is too strong.
Mechanisms of the Tropical Upwelling Branch of the Brewer–Dobson Circulation: The Role of Extratropical Waves
Authors: Chen Gang , Sun Lantao
Published: June 2011

The role of extratropical waves in the tropical upwelling branch of the Brewer–Dobson circulation is investigated in an idealized model of the stratosphere and troposphere. To simulate different stratospheric seasonal cycles of planetary waves in the two hemispheres, seasonally varying radiative heating is imposed only in the stratosphere, and surface topographic forcing is prescribed only in the Northern Hemisphere (NH). A zonally symmetric version of the same model is used to diagnose the effects of different wavenumbers and different regions of the total forcing on tropical stratospheric upwelling.

The simple configuration can simulate a reasonable seasonal cycle of the tropical upwelling in the lower stratosphere with a stronger amplitude in January (NH midwinter) than in July (NH midsummer), as in the observations. It is shown that the seasonal cycle of stratospheric planetary waves and tropical upwelling responds nonlinearly to the strength of the tropospheric forcing, with a midwinter maximum under strong NH-like tropospheric forcing and double peaks in the fall and spring under weak Southern Hemisphere (SH)-like forcing. The planetary wave component of the total forcing can approximately reproduce the seasonal cycle of tropical stratospheric upwelling in the zonally symmetric model.

The zonally symmetric model further demonstrates that the planetary wave forcing in the winter tropical and subtropical stratosphere contributes most to the seasonal cycle of tropical stratospheric upwelling, rather than the high-latitude wave forcing. This suggests that the planetary wave forcing, prescribed mostly in the extratropics in the model, has to propagate equatorward into the subtropical latitudes to induce sufficient tropical upwelling. Another interesting finding is that the planetary waves in the summer lower stratosphere can drive a shallow residual circulation rising in the subtropics and subsiding in the extratropics.
Lateral Mixing in the Pycnocline by Baroclinic Mixed Layer Eddies
Authors: Badin Gualtiero , Tandon Amit , Mahadevan Amala
Published: June 2011

Using a process study model, the effect of mixed layer submesoscale instabilities on the lateral mixing of passive tracers in the pycnocline is explored. Mixed layer eddies that are generated from the baroclinic instability of a front within the mixed layer are found to penetrate into the pycnocline leading to an eddying flow field that acts to mix properties laterally along isopycnal surfaces. The mixing of passive tracers released on such isopycnal surfaces is quantified by estimating the variance of the tracer distribution over time. The evolution of the tracer variance reveals that the flow undergoes three different turbulent regimes. The first regime, lasting about 3–4 days (about 5 inertial periods) exhibits near-diffusive behavior; dispersion of the tracer grows nearly linearly with time. In the second regime, which lasts for about 10 days (about 14 inertial periods), tracer dispersion exhibits exponential growth because of the integrated action of high strain rates created by the instabilities. In the third regime, tracer dispersion follows Richardson’s power law. The Nakamura effective diffusivity is used to study the role of individual dynamical filaments in lateral mixing. The filaments, which carry a high concentration of tracer, are characterized by the coincidence of large horizontal strain rate with large vertical vorticity. Within filaments, tracer is sheared without being dispersed, and consequently the effective diffusivity is small in filaments. While the filament centers act as barriers to transport, eddy fluxes are enhanced at the filament edges where gradients are large.
Concerted Cultivation? Parenting Values, Education and Class Diversity
Authors: Irwin Sarah , Elley Sharon
Published: June 2011

The article presents an analysis of new empirical evidence on parenting values and orientations to children’s education and social class. A survey of parents with children involved in organized activities was undertaken, followed by a series of semi-structured interviews with a sample strategically identified with reference to both social class and subjective orientations to education. We argue that within recent literature there has been a tendency towards overstating the internal homogeneity of middle-class and working-class experiences. Our data reveal diverse parental orientations to their children’s education within, as well as across, classes. We analyse this diversity in relation to varied circumstances, and draw out some implications for theories of inequality.
Young Women, Class and Gendered Heterosexuality: The Implication of Educational Aspirations and Social Networks for Sex Education Messages
Authors: Elley Sharon
Published: June 2011

This article reports findings from an ESRC-funded investigation into the interface between Sex and Relationship Education (hereafter SRE) and young people’s experiences as mediated by the interconnections of class, gender and heterosexuality. The article focuses on how young women’s gendered heterosexual practices, alongside educational aspirations, are given meaning by the values embedded in classed circumstances, social networks and relationships. Developing a ‘relational’ approach, the conceptual framework combines different levels of analysis and complicates the idea of a simple workingclass/middle-class dichotomy. The empirical data are drawn from one-to-one interviews and focus groups with 69 young people, aged 15 to 21 years old, although only women’s narratives are presented. I argue that understanding how young people draw on normative discourses about gendered heterosexuality, as well as class-related practices and aspirations as embedded in particular social networks, provides greater insight into theorizing the regulation of sexual identities as linked to SRE messages.
The Prosumer and the Project Studio: The Battle for Distinction in the Field of Music Recording
Authors: Cole Steven James
Published: June 2011

Using participant observation and content analysis of musicians’ internet newsgroups and bulletin boards, my research examines the creation of a new socio-historic subject (‘the prosumer’) and space of production (‘the project studio’). Prosumers’ practices illustrate a nondeterministic form of structural causation that both supports and refutes Bourdieu’s theory of cultural/social (re)production. In support of Bourdieu, my empirical research illustrates the relative autonomy of the habitus and shows that cultural production can foster social change. Although Bourdieu repeatedly made such theoretical claims, his struggle to empirically support them led critics to characterize his work as a synchronously reproductive form of economic reductionism. While I reject these critiques, my work does problematize Bourdieu’s understanding of ‘capital conversion’ and complicates his somewhat ‘straightforward’ relation of cultural practice to economic class. Such ‘relations and conversions’ presuppose clearly separated economic/cultural and productive/ consumptive social spheres. Since ‘prosumption’ blurs these demarcations, we must subsequently reassess aspects of Bourdieu’s work.
Pharmacokinetics and Pharmacodynamics of Aliskiren/Hydrochlorothiazide Single‐Pill Combination Tablets and Free Combination of Aliskiren and Hydrochlorothiazide
Authors: Yan Jing‐He , Jarugula Venkateswar , Sabo Ron , Papst Cheraz Cherif , Zhang Jack , Dole William P.
Published: June 2011

Single‐pill combinations (SPCs) of complementary antihypertensive agents provide patients with a simple and effective treatment regimen. To ensure that the efficacy and safety of an SPC is the same as that for the individual drugs administered together (free combination), SPC and free‐combination formulations must be shown to be bioequivalent. Three open‐label, randomized studies compared the pharmacokinetics of SPC tablets of the direct renin inhibitor aliskiren and hydrochlorothiazide (HCT), at doses of 150/25, 300/12.5, and 300/25 mg, with the corresponding free combinations in healthy volunteers. Data from 2 randomized, double‐blinded studies of patients with hypertension were used to assess inhibition of plasma renin activity (PRA) by the aliskiren/HCT 300/25 mg SPC and the free combination. At all dose combinations, aliskiren and HCT systemic drug exposure was similar when administered as an SPC or free combination, indicating bioequivalence. Aliskiren/HCT 300/25 mg SPC inhibited PRA to the same extent as the free combination. HCT alone increased PRA through activation of the renin‐angiotensin system; aliskiren prevented this diuretic‐induced increase to the same extent when administered as the free combination or as the SPC. In conclusion, aliskiren/HCT SPCs are pharmacokinetically and pharmacodynamically bioequivalent to aliskiren and HCT in free combination.
Characterization of the Human QT Interval: Novel Distribution‐Based Assessment of the Repolarization Effects of Moxifloxacin
Authors: Holzgrefe Henry H. , Ferber Georg , Morrison Royce , Meyer Olivier , Greiter‐Wilke Andrea , Singer Thomas
Published: June 2011

The authors have previously demonstrated rate‐independent QT variability in the dog and cynomolgus monkey, where the QT associated with any RR was a normally distributed value that was accurately evaluated as the distribution mean. The present study investigated the rate‐independent characteristics of the human QT. Digital electrocardiographs (1000 Hz) were collected for 24 hours in 51 patients (thorough QT study) and analyzed by computer. Distribution‐based analysis was applied to the placebo and moxifloxacin (400 mg) arms to characterize the nature of the QT interval and to assess the efficacy of distribution‐based analysis for QTc determination. Novel statistics using continuous means and bootstrapped 95% confidence intervals were developed to facilitate QT analysis. Machine‐read QT values were compared with core laboratory semiautomated values for verification. RR intervals demonstrated repetitive protocol‐dependent variations (50–250 milliseconds); QT intervals were normally distributed, spanning 60 to 100 milliseconds for each RR interval. Distribution‐based analysis detected a moxifloxacin response identical to semiautomated analysis, but with reduced variability and improved statistical power, where n = 12 satisfied the ICH E14 criteria for a positive control. Distribution‐based analysis has the potential to provide a universal method for clinical QT heart rate correction, enabling accurate detection of QT changes when limited numbers of volunteers are exposed to drug.
Tympanic Membrane Rupture in the Survivors of the July 7, 2005, London Bombings
Authors: Radford Peter , Patel Hasu D. L. , Hamilton Nicholas , Collins Mark , Dryden Steven
Published: June 2011

Objective

The goal of this study was to analyze the prevalence of tympanic membrane rupture in the survivors of the London bombings of July 2005 and to assess whether tympanic membrane rupture provides a useful biomarker for underlying primary blast injuries.

Study Design

Cross‐sectional study.

Subjects and Methods

Survivors of the 4 blasts of London bombings on July 7, 2005. Data were gathered from medical records and the London’s Metropolitan Police evidence documenting the injuries sustained by 143 survivors of the blasts. All patients with tympanic membrane rupture or primary blast injury were indentified. Analysis was made of distance against prevalence of tympanic membrane rupture. Correlation between tympanic membrane rupture and other forms of primary blast injury was then assessed.

Results

Results from the 143 survivors showed a 48% prevalence of tympanic membrane rupture across all 4 sites. Fifty‐one patients had isolated tympanic membrane rupture with no other primary blast injuries. Eleven patients had tympanic membrane rupture and other primary blast injuries, but only one of these was an initially concealed injury (blast lung).

Conclusions

Tympanic membrane rupture in survivors of the London bombings on July 7, 2005, had a high prevalence affecting half of patients across a range of distances from the blasts. Tympanic membrane did not act as an effective biomarker of underlying blast lung. In a mass casualty event, patients with isolated tympanic membrane rupture with normal observations and chest radiography can be monitored for a short period and safely discharged with arrangement for ear, nose, and throat follow‐up.
Older people in unfamiliar environments: Assimilating a multi-disciplinary literature to a planning problem
Authors: Spaul Martin , Hockey Ann
Published: June 2011

This article considers aspects of the assimilation of academic research to town planning guidelines and policies, in particular research conducted in terms, and with methodologies, remote from practical town planning processes. It grew out of an interdisciplinary project examining the experience of older people in unfamiliar spaces, and drew on a wide literature dealing with spatial experience from a range of perspectives. The project sought to retrieve a set of outcomes from the interdisciplinary environment of enquiry for use in the town planning process, requiring the translation of a complex knowledge base to a clear framework, and raising issues about how the richness and diversity of the original research might be preserved during this process. The article concludes that the straightforward translation of knowledge from a range of disciplines into practical policy outcomes cannot reasonably be achieved without a re-consideration of the scope of policy-related discourse.