bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing Clerical Efforts To Secure Lay Support in the Flacian Controversy Over Original Sin
Authors: Christman Robert J.
Published: July 2010

In the decades following Luther's death, adherents of the Wittenberg Reformation fought amongst themselves over how to define the reformer's theology. Often such struggles pitted Philippists against Gnesio-Lutherans, but sometimes the controversies took place within these groups themselves. The following article examines the Flacian controversy over original sin as it split the Gnesio-Lutheran pastorate of the central German county of Mansfeld. Rather than focusing on the content of the debate, this study analyzes the two distinct approaches to the laity taken by the pastors on each side of the divide. One side endeavored to present the doctrinal complexities of the disagreement to the parishioners; the other attempted to shield the laity from the intricacies of the dispute. It was, therefore, not only a theological disagreement that divided the pastors, but two distinct and competing visions of ecclesiology and the role of the laity in the church.
Preaching Calvinism in Lutheran Danzig: Jacob Fabritius On the Pastoral Office
Authors: Tode Sven
Published: July 2010

Jacob Fabritius was the director of the Danzig academy for almost 50 years and therefore determined the confessional identity of Danzig's pastors, who were recruited chiefly from the Latin school over a long period of time. At the same time, Fabritius was a champion of Calvinism in the predominantly Lutheran city of Danzig. This paper analyses Fabritius's programmatic sermon, given on October 24, 1596, in which he developed his understanding of the office and importance of the pastor, urged confessional unity amid the diversity of non-Catholics, and placed the pastors between the commune and the magistrate as apostles sent by God. Analysis of this sermon provides new insights into the relation between clerical and secular authorities and calls attention to the various ways in which sermons can be interpreted. Attention to these ways of interpretation contributes to a wider understanding of the structures of early modern society.
"The Care of Souls Is a Very Grave Burden for [the Pastor]": Professionalization of Clergy in Early Modern Florence, Lucca, and Arezzo
Authors: Comerford Kathleen M.
Published: July 2010

Councils and bishops in late sixteenth- and early seventeenth-century Tuscan dioceses emphasized vocation and the cura animarurn in their efforts to reform the parish clergy after the Council of Trent. The desired criteria for pastoral behavior were relatively simple, yet in many instances conformity was elusive. While synods and visitations clearly articulate a vision of professionalism, and even state penalties for failures to achieve that vision, most parishes display instead a continuation of prior practices in several important areas, including very low levels of conformity with Tridentine and post-Tridentine reglations concerning education of priests and availability of up-to-date service books. Since the penalties were relatively small, and often did not produce any change, historians may conclude that seventeenth-century priests were not able to achieve the level of professionalization desired of them.
Estimation of Climate-Change Impacts on the Urban Heat Load Using an Urban Climate Model and Regional Climate Projections
Authors: Früh Barbara , Becker Paul , Deutschländer Thomas , Hessel Johann-Dirk , Kossmann Meinolf , Mieskes Ingrid , Namyslo Joachim , Roos Marita , Sievers Uwe , Steigerwald Thomas , Turau Heidelore , Wienert Uwe
Published: July 2010

A pragmatic approach to estimate the impact of climate change on the urban environment, here called the cuboid method, is presented. This method allows one to simulate the urban heat load and the frequency of air temperature threshold exceedances using only eight microscale urban climate simulations for each relevant wind direction and time series of daily meteorological parameters either from observations or regional climate projections. Eight representative simulations are designed to encompass all major potential urban heat-stress conditions. From these representative simulations, the urban-heat-load conditions in any weather situation are derived by interpolation. The presented approach is applied to study possible future heat load in Frankfurt, Germany, using the high-resolution Microscale Urban Climate Model in three dimensions (MUKLIMO_3). To estimate future changes in heat-load-related climate indices in Frankfurt, climate projections from the regional climate models Max Planck Institute Regional Model (REMO), Climate Limited-Area Model (CLM), Wetterlagen-basierte Regionalisierungsmethode (WETTREG), and Statistical Regional Model (STAR) are used. These regional climate models are driven by the “ECHAM5” general circulation model and Intergovernmental Panel on Climate Change emission scenario A1B. For the mean annual number of days with a maximum daily temperature exceeding 25°C, a comparison between the cuboid method results from observed and projected regional climate time series of the period 1971–2000 shows good agreement, except for CLM for which a clear underestimation is found. On the basis of the 90% significance level of all four regional climate models, the mean annual number of days with a maximum daily temperature exceeding 25°C in Frankfurt is expected to increase by 5–32 days for 2021–50 as compared with 1971–2000.
Mesoscale Modeling of Boundary Layer Refractivity and Atmospheric Ducting
Authors: Haack Tracy , Wang Changgui , Garrett Sally , Glazer Anna , Mailhot Jocelyn , Marshall Robert
Published: July 2010

In this study four mesoscale forecasting systems were used to investigate the four-dimensional structure of atmospheric refractivity and ducting layers that occur within evolving synoptic conditions over the eastern seaboard of the United States. The aim of this study was to identify the most important components of forecasting systems that contribute to refractive structures simulated in a littoral environment. Over a 7-day period in April–May of 2000 near Wallops Island, Virginia, meteorological parameters at the ocean surface and within the marine atmospheric boundary layer (MABL) were measured to characterize the spatiotemporal variability contributing to ducting. By using traditional statistical metrics to gauge performance, the models were found to generally overpredict MABL moisture, resulting in fewer and weaker ducts than were diagnosed from vertical profile observations. Mesoscale features in ducting were linked to highly resolved sea surface temperature forcing and associated changes in surface stability and to local variations in internal boundary layers that developed during periods of offshore flow. Sensitivity tests that permit greater mesoscale detail to develop on the model grids revealed that initialization of the simulations and the resolution of sea surface temperature analyses were critical factors for accurate predictions of coastal refractivity.
On the Dynamics of Two-Dimensional Hurricane-Like Vortex Symmetrization
Authors: Martinez Y. , Brunet G. , Yau M. K.
Published: July 2010

Despite the fact that asymmetries in hurricanes, such as spiral rainbands, polygonal eyewalls, and mesovortices, have long been observed in radar and satellite imagery, many aspects of their origin, space–time structure, and dynamics still remain unsolved, particularly their role on the vortex intensification. The underlying inner-core dynamics need to be better understood to improve the science of hurricane intensity forecasting. To fill this gap, a simple 2D barotropic “dry” model is used to perform two experiments starting respectively with a monopole and a ring of enhanced vorticity to mimic hurricane-like vortices during incipient and mature stages of development. The empirical normal mode (ENM) technique, together with the Eliassen–Palm (EP) flux calculations, are used to isolate wave modes from the model datasets to investigate their space–time structure, kinematics, and the impact on the changes in the structure and intensity of the simulated hurricane-like vortices.

From the ENM diagnostics, it is shown in the first experiment how an incipient storm described by a vortex monopole intensifies by “inviscid damping” of a “discrete-like” vortex Rossby wave (VRW) or quasi mode. The critical radius, the structure, and the propagating properties of the quasi mode are found to be consistent with predictions of the linear eigenmode analysis of small perturbations. In the second experiment, the fastest growing wavenumber-4 unstable VRW modes of a vortex ring reminiscent of a mature hurricane are extracted, and their relation with the polygonal eyewalls, mesovortices, and the asymmetric eyewall contraction are established in consistency with results previously obtained from other authors.
Stratified Inertial Subrange Inferred from In Situ Measurements in the Bottom Boundary Layer of the Rockall Channel
Authors: Bouruet-Aubertot Pascale , van Haren Hans , Lelong M. Pascale
Published: July 2010

Deep-ocean high-resolution moored temperature data are analyzed with a focus on superbuoyant frequencies. A local Taylor hypothesis based on the horizontal velocity averaged over 2 h is used to infer horizontal wavenumber spectra of temperature variance. The inertial subrange extends over fairly low horizontal wavenumbers, typically within 2 × 10−3 and 2 × 10−1 cycles per minute (cpm). It is therefore interpreted as a stratified inertial subrange for most of this wavenumber interval, whereas in some cases the convective inertial subrange is resolved as well. Kinetic energy dissipation rate ε is inferred using theoretical expressions for the stratified inertial subrange. A wide range of values within 10−9 and 4 × 10−7 m2 s−3 is obtained for time periods either dominated by semidiurnal tides or by significant subinertial variability. A scaling for ε that depends on the potential energy within the inertio-gravity waves (IGW) frequency band PEIGW and the buoyancy frequency N is proposed for these two cases. When semidiurnal tides dominate, ε ≃ (PEIGWN)3/2, whereas ε ≃ PEIGWN in the presence of significant subinertial variability. This result is obtained for energy levels ranging from 1 to 30 times the Garrett–Munk energy level and is in contrast with classical finescale parameterization in which ε ∼ (PEIGW)2 that applies far from energy sources. The specificities of the stratified bottom boundary layer, namely a weak stratification, may account for this difference.
Making Sense of Voices: An Exploration of Meaningfulness in Auditory Hallucinations in Schizophrenia
Authors: Suri Rochelle
Published: July 2010

This article is a qualitative exploration of how auditory hallucinations have been experienced as meaningful to individuals diagnosed with schizophrenia. This theoretical perspective is supported by the survey of the literature, which suggests that for many centuries, individuals experiencing auditory hallucinations have been given much more credence than their counterparts in modern society. Most recent studies on auditory hallucinations indicate that auditory hallucinations themselves are not debilitating. Romme proposes instead that the fear of not being able to control or manage the auditory hallucinations can be disabling to the individual. Using a case example from the author’s own work, as well as drawing from other researchers and theorists, the article provides concrete illustrations of how individuals have derived insight from their auditory hallucinations. It is expected that the article may help clinicians better understand auditory hallucinations in schizophrenia, particularly with regard to clinical treatment, as well as shed light on the phenomena of auditory hallucinations.
Suitability of a Rare Earth Organic Light Conversion Agent of Eu(III) Complex to Improve Ultraviolet Protection Properties of Cotton Fabrics
Authors: Zhihua Chen  , Guibo Yin
Published: July 2010

Light conversion agents (LCAs) have the ability to absorb ultraviolet radiation (UV) and emit visible light. With their light conversion mechanism, LCAs can be used to engineer protective textiles. This study investigates the feasibility of using LCAs as UV blocking finishes. The activity of LCAs was firstly studied, then LCAs were used to produce the protective fabrics, and finally the level of UV protection of the treated fabrics was tested. Measuring results revealed that rare earth organic complex light conversion agents can absorb 300—360 nm ultraviolet radiation and emit red and yellow light. The treated fabrics demonstrated excellent ultraviolet protective properties with an LCA dosage of 10 g/L. At this dosage, the ultraviolet protection factor (UPF) value was enhanced 8 times and the decrease rate of the transmittance for UVA and UVB was over 86.2%, which suggests that LCAs are good potential candidates for the UV protection finishes of textiles.
An Update of a Classic
Authors: Lambright Kristina T.
Published: July 2010

This study explores whether a classic motivation theory traditionally applied by public administration scholars in bureaucratic settings can also be used to understand relationships in intersectoral service delivery networks. It focuses on how well expectancy theory explains contracted provider motivation to properly use service-monitoring tools because of contract rewards and penalties. To examine this question, qualitative data were collected from early childhood programs in three communities. Expectancy theory in its current form does not do a good job consistently explaining contracted provider motivation. An expanded version of the theory may be more useful in situations where there is uncertainty.
TRPV1 receptor blockade is ineffective in different in vivo models of migraine
Authors: Summ Oliver , Holland Philip R , Akerman Simon , Goadsby Peter J
Published: July 2010

Background: It has been proposed that TRPV1 receptors may play a role modulating trigeminal sensory processing. We used models of trigeminovascular nociceptive activation to study the involvement of TRPV1 receptors in the rat. Due to a possible role of TRPV1 receptors in cortical spreading depression (CSD), an experimental phenomenon sharing many features with migraine aura, we also utilized a model of mechanically induced CSD.

Methods: Male Sprague Dawley rats ( N = 39) were anesthetized and cannulated for monitoring and drug administration to study the effects of the TRPV1 receptor antagonist A-993610 (8 mg kg−1 IV). Wide-dynamic-range neurons, responding to electrical stimulation of the middle meningeal artery (MMA)/dura mater were identified and recorded using electrophysiological techniques. Intravital microscopy was used to study neurogenic dural vasodilation (NDV) of the MMA comparing capsaicin and electrical stimulation, and the effect of A-993610 on mechanically induced CSD was examined.

Results: Administration of A-993610 had no significant effect on trigeminal firing of A- or C-fibers elicited by electrical stimulation of the MMA. It also showed no effect on NDV whilst blocking vasodilation due to intravenous capsaicin injection. The mechanically induced CSD response could not be altered by A-993610 administration.

Conclusions: Although there is evidence that TRPV1 receptors play an important role in sensory processing in general, the new data do not support a role in the treatment of acute migraine.
Generalized Joint Hypermobility and Risk of Lower Limb Joint Injury During Sport
Authors: Pacey Verity , Nicholson Leslie L. , Adams Roger D. , Munn Joanne , Munns Craig F.
Published: July 2010

Background: Generalized joint hypermobility is a highly prevalent condition commonly associated with joint injuries. The current literature has conflicting reports of the risk of joint injury in hypermobile sporting participants compared with their nonhypermobile peers. Systematic reviews have not been conclusive and no meta-analysis has been performed.

Purpose: This review was undertaken to determine whether individuals with generalized joint hypermobility have an increased risk of lower limb joint injury when undertaking sporting activities.

Study Design: Systematic review with meta-analysis.

Methods: Studies were identified through a search without language restrictions of PubMed, CINAHL, Embase, and SportDiscus databases from the earliest date through February 2009 with subsequent handsearching of reference lists. Inclusion criteria for studies were determined before searching and all included studies underwent methodological quality assessment by 2 independent reviewers. Meta-analyses for joint injury of the lower limb, knee, and ankle were performed using a random effects model. The difference in injury proportions between hypermobility categories was tested with the z statistic.

Results: Of 4841 identified studies, 18 met all inclusion criteria with methodological quality ranging from 1 of 6 to 5 of 6. A variety of tests of hypermobility and varied cutoff points to define the presence of generalized joint hypermobility were used, so the authors determined a standardized cutoff to indicate generalized joint hypermobility. Using this criterion, a significantly increased risk of knee joint injury for hypermobile and extremely hypermobile participants compared with their nonhypermobile peers was demonstrated ( P < .001), whereas no increased risk was found for ankle joint injury. For knee joint injury, a combined odds ratio of 4.69 (95% confidence interval, 1.33-16.52; P = .02) was calculated, indicating a significantly increased risk for hypermobile participants playing contact sports.

Conclusion: Sport participants with generalized joint hypermobility have an increased risk of knee joint injury during contact activities but have no altered risk of ankle joint injury.
The Biomechanics of Medial Patellofemoral Ligament Repair Followed by Lateral Retinacular Release
Authors: Bedi Harvinder , Marzo John
Published: July 2010

Background: Repair of the medial patellofemoral ligament (MPFL) for acute patellar instability has recently become popular, with good clinical success rates reported in the literature. Usually, a lateral retinacular release (LRR) is added to the medial repair in an effort to “rebalance” the patella. In the native knee, however, isolated LRR reduces the force required to displace the patella laterally and may be an undesirable component of instability surgery.

Hypothesis: The authors’ hypothesis was that LRR, when performed after MPFL repair, would reduce the force required to displace the patella laterally.

Study Design: Controlled laboratory study.

Methods: Eight fresh-frozen human cadaveric knees were prepared as a model for acute patellar dislocation by transecting the MPFL at its patellar attachment. The knees were sequentially tested in the native (control), cut MPFL, repaired MPFL, and repaired MPFL with LRR conditions. Each knee was mounted and tested on an MTS machine that measured the amount of force required to displace the patella 1 cm laterally. Testing was done at 0°, 15°, 30°, 45°, and 60° of knee flexion.

Results: Cutting the MPFL reduced the force required to displace the patella 1 cm laterally by 14% to 22% compared with the native knee. Repair of the ligament restored the ability of the patella to resist lateral force. Adding a lateral release to the repair reduced the force required to displace the patella 1 cm by 7% to 11% compared with the MPFL-repaired knee.

Conclusion: After repair of the MPFL, adding an LRR lowered the ability of the patella to resist lateral displacement.

Clinical Relevance: According to this study, LRR may not be routinely appropriate as a part of the stabilizing procedure to address acute patellar dislocation when the MPFL is avulsed from the patella.
A case study of two schools: identifying core values conducive to the building of a positive school culture
Authors: Lance Ann
Published: July 2010

This article is based on a case study of two ethnically diverse urban primary schools in England. Both schools have been recognised locally and nationally for their engagement in projects which exemplify innovative practice. The article traces the impact of school effectiveness and improvement theory on primary schools in England, identifying an ethical approach to leadership as a critical factor. It seeks to explore evidence of the values which underpinned the practice within the two case study schools. The commitment of the headteachers to their individual schools, their respect for the pupils and their families and their attention to providing a breadth of learning experience are identified as being key factors. Further research into the critical role which positive values play in pedagogical reform is suggested.
Household Projection and Its Application to Health/Long-Term Care Expenditures in Japan Using INAHSIM-II
Authors: Fukawa Tetsuo
Published: July 2010

Using a microsimulation model named Integrated Analytical Model for Household Simulation (INAHSIM), the author conducted a household projection in Japan for the period of 2010—2050. INAHSIM-II specifically means that the initial population is created using the INAHSIM model itself. The model produces outputs such as (a) the number of the elderly according to dependency and/or living situations, (b) the relative parents/children ratio taking into account the number of brothers and sisters, and (c) a 1-year transition matrix by household type. As an application of the model, a projection of health and long-term care expenditures is made for the years 2010—2050 in Japan.
A comparison and integration of tree-ring and alluvial records of fire history at the Missionary Ridge Fire, Durango, Colorado, USA
Authors: Bigio Erica , Swetnam Thomas W. , Baisan Christopher H.
Published: July 2010

We used tree-ring and alluvial sediment methods to reconstruct past fire regimes for a mixed conifer forest within a 1 km2 drainage basin which was severely burned by a wildfire near Durango, Colorado. Post-fire debris flow events incised the valley-filling alluvial sediments in the lower basin, and created exposures of fire-related of deposits of late-Holocene age. Tree-ring and alluvial sediment fire history records were created separately, and then compared and integrated to create a ~ 3000 year record of past fire activity. The tree-ring record showed that from AD 1679 to 1879, there were frequent surface fires, while patches of high-severity fire occurred during widespread fire years. The alluvial record showed that a low- to moderate-and mixed-severity fire regime has likely been dominant over the past ~ 2600 calibrated calendar years before present, as shown by locally episodic deposition of charcoal-rich, fine-grained sediments. Radiocarbon dating suggested that in two stratigraphic sections, there was rapid deposition of several fine-grained sediment layers. One of these episodes occurred during the Medieval Climatic Anomaly (AD 900—1300). A charcoal-rich debris flow deposit in the oldest exposed part of the stratigraphic record dated to ~ 2600 calibrated calendar years before present. This event was potentially equivalent in magnitude to the debris-flow events following the recent wildfire in the study area, and is evidence of a high-severity fire that burned a large proportion of the study basin. The timing of this event coincides with a period of less frequent, yet more severe wildfires in a nearby lake sediment record, and is associated with the end of a Neoglacial period of cooler and wetter temperatures.
Review: The New Concept of ‘‘Interventional Heart Failure Therapy’’: Part 2—Inotropes, Valvular Disease, Pumps, and Transplantation
Authors: Thompson Keith A. , Philip Kiran J. , Simsir Sinan , Schwarz Ernst R.
Published: July 2010

Recent advances in heart failure therapy include a variety of mechanical and device-based technologies that target structural aspects of heart failure that cannot be treated with drug therapy alone; these newer therapies can collectively be described as interventional heart failure therapy. This article is the second in a 2-part series reviewing interventional heart failure therapy. Interventions included in this discussion include those indicated for the treatment of end-stage refractory heart failure, including interventional medical therapy, interventional treatment of valvular disease, mechanical assist devices, and heart transplantation. Also included is a review of the currently available catheter-based pumps, which are intended to provide temporary support in patients with acute hemodynamic compromise. The use of cellular or stem cell therapy for the treatment of heart failure is an emerging interventional therapy and data supporting its use for the treatment heart failure will also be presented, as will a discussion of the role of palliative care and self-care in heart failure therapy.
Review: Autophagy: Definition, Molecular Machinery, and Potential Role in Myocardial Ischemia-Reperfusion Injury
Authors: Dong Yi , Undyala Vishnu V. , Gottlieb Roberta A. , Mentzer Robert M. , Przyklenk Karin
Published: July 2010

Autophagy is the endogenous, tightly regulated cellular "housekeeping" process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates. There is a growing consensus that autophagy is upregulated in the setting of myocardial ischemia-reperfusion. Moreover, emerging data suggest that autophagy may serve as an adaptive process and confer increased resistance to ischemia-reperfusion injury. Our aims in this review are to (1) provide a brief synopsis of process of autophagy (including an overview of the key molecular mediators of this catabolic process and its relationship with other cardiac signaling pathways) and (2) most importantly, summarize the current evidence for versus against the intriguing concept of autophagy-mediated cardioprotection.
High-performance Physics Simulations Using Multi-core CPUs and GPGPUs in a Volunteer Computing Context
Authors: Karimi Kamran , Dickson Neil , Hamze Firas
Published: July 2010

This paper presents two conceptually simple methods for parallelizing a Parallel Tempering Monte Carlo simulation in a distributed volunteer computing context, where computers belonging to the general public are used. The first method uses conventional multi-threading. The second method uses CUDA, a graphics card computing system. Parallel Tempering is described, and challenges such as parallel random number generation and mapping of Monte Carlo chains to different threads are explained. While conventional multi-threading on central processing units is well-established, GPGPU programming techniques and technologies are still developing and present several challenges, such as the effective use of a relatively large number of threads. Having multiple chains in Parallel Tempering allows parallelization in a manner that is similar to the serial algorithm. Volunteer computing introduces important constraints to high performance computing, and we show that both versions of the application are able to adapt themselves to the varying and unpredictable computing resources of volunteers’ computers, while leaving the machines responsive enough to use. We present experiments to show the scalable performance of these two approaches, and indicate that the efficiency of the methods increases with bigger problem sizes.
Collection and processing of whole blood for transformation of peripheral blood mononuclear cells and extraction of DNA: the Type 1 Diabetes Genetics Consortium
Authors: Rosinger Silke , Nutland Sarah , Mickelson Eric , Varney Michael D , Boehm Bernard O , Olsem Gary J , Hansen John A , Nicholson Ian , Hilner Joan E , Perdue Letitia H , Pierce June J , Akolkar Beena , Nierras Concepcion , Steffes Michael W ,   T1DGC
Published: July 2010

Background and Purpose To yield large amounts of DNA for many genotype analyses and to provide a renewable source of DNA, the Type 1 Diabetes Genetics Consortium (T1DGC) harvested DNA and peripheral blood mononuclear cells (PBMCs) from individuals with type 1 diabetes and their family members in several regions of the world.

Methods DNA repositories were established in Asia-Pacific, Europe, North America, and the United Kingdom. To address region-specific needs, different methods and sample processing techniques were used among the laboratories to extract and to quantify DNA and to establish Epstein-Barr virus transformed cell lines.

Results More than 98% of the samples of PBMCs were successfully transformed. Approximately 20—25 μg of DNA were extracted per mL of whole blood. Extraction of DNA from the cell pack ranged from 92 to 165 μg per cell pack. In addition, the extracted DNA from whole blood or transformed cells was successfully utilized in each regional human leukocyte antigen genotyping laboratory and by several additional laboratories performing consortium-wide genotyping projects.

Limitations Although the isolation of PBMCs was consistent among sites, the measurement of DNA was difficult to harmonize.

Conclusions DNA repositories can be established in different regions of the world and produce similar amounts of high-quality DNA for a variety of high-throughput genotyping techniques. Furthermore, even with the distances and time necessary for transportation, highly efficient transformation of PBMCs is possible. For future studies/trials involving several laboratories in different locations, the T1DGC experience includes examples of protocols that may be applicable. In summary, T1DGC has developed protocols that would be of interest to any scientific organization attempting to overcome the logistical problems associated with studies/trials spanning multiple research facilities, located in different regions of the world. Clinical Trials 2010; 7: S65—S74. http://ctj.sagepub.com
Women in Academic Administration at the University
Authors: Tomàs Marina , Lavie Jose Manuel , Duran Maria del Mar , Guillamon Cristina
Published: July 2010

In this article we summarize the most relevant findings from a research study that endeavours to incorporate a gender perspective in the study of university administration. The study analyses the role of women in both horizontal and vertical administrative structures in four Catalan universities, taking into account their expectations and perceptions. Overall, the results point to the existence of both external and internal barriers that explain the lack of women in university administration. Among these barriers, organizational culture appears as a change-resistant element that promotes an environment dominated by male values and justifies most women’s self-exclusion from university administration. The study also identifies the main features of how these women depict their experiences in administration and attempts to articulate an alternative discourse for leadership at the university.
Choosing chemotherapy in patients with advanced urothelial cell cancer who are unfit to receive cisplatin-based chemotherapy
Authors: de Vos F.Y.F.L. , de Wit R.
Published: July 2010

Transitional cell carcinoma of the urothelial tract is the second most common cancer of the genitourinary system and the fifth most common cancer in Western countries with more than 300,000 new cases per year worldwide. Following the introduction of cisplatin-based chemotherapy, median overall survival in patients with metastatic disease has doubled, demonstrating chemotherapy as an important treatment modality in advanced or metastatic disease. Patients ‘unfit’ to receive cisplatin-based chemotherapy are characterized by impaired renal function, impaired performance status, and/or comorbidity that preclude the use of cisplatin. In this review we summarize the different chemotherapeutic schemes, focusing on treatment options in cisplatin ‘unfit’ patients.
A population-based study of cardiac morbidity among Hodgkin lymphoma patients with preexisting heart disease
Authors: Myrehaug Sten , Pintilie Melania , Yun Lingsong , Crump Michael , Tsang Richard W. , Meyer Ralph M. , Sussman Jonathan , Yu Eric , Hodgson David C.
Published: July 2010

The risk of cardiac hospitalization (CH) in Hodgkin lymphoma (HL) patients with preexisting heart disease was evaluated. Patients with HL were identified from a population-based registry (N = 3964). Data were abstracted from records of a randomly selected subcohort (N = 1096). A population-based registry was used to identify CH. Factors associated with CH and the incidence of CH after HL were estimated with competing risk models. Preexisting heart disease was the strongest predictor of posttreatment CH (hazard ratio = 3.98, P < .001) and significantly modified (P = .01) the effect of treatment on the risk of CH. Among patients with preexisting heart disease, treatment with mediastinal radiation therapy plus doxorubicin-based chemotherapy was associated with a 10-year incidence of CH more than 20% higher than treatment with chemotherapy alone. There is a high risk of CH after mediastinal radiation therapy plus doxorubicin-based chemotherapy among patients with preexisting heart disease; this is an important consideration when weighing treatment options, and in the follow-up of these patients.
Collagen remodelling by airway smooth muscle is resistant to steroids and β2-agonists
Authors: Bourke J.E. , Li X. , Foster S.R. , Wee E. , Dagher H. , Ziogas J. , Harris T. , Bonacci J.V. , Stewart A.G.
Published: July 2010

Bi-directional interactions between airway smooth muscle (ASM) and the altered extracellular matrix (ECM) may influence airway wall remodelling and ASM function in asthma. We have investigated the capacity of cultured human ASM to reorganise the structure of three-dimensional collagen gels and the effects of endothelin (ET)-1 and agents used to treat asthma.

Human ASM cells were cast in type I collagen gels. Reductions in gel area over 72 h were determined in the absence and presence of ET-1 and potential inhibitors, steroids and β2-adrenoceptor agonists. Changes in gel wet weights and hydroxyproline content were measured and ASM gel morphology was examined by scanning electron microscopy.

Cell density-dependent reductions in gel area were augmented by ET-1, mediatedviaETAreceptors. This process was not associated with ASM contraction or proliferation, but was consistent with ASM tractional remodelling and migration leading to collagen condensation rather than collagen degradation within gels. The collagen remodelling by ASM was unaffected by salbutamol and/or budesonide.

This study demonstrates an additional potential role for ASM in ECM regulation and dysregulation in airways disease that is resistant to steroids and β2-adrenoceptor agonists. Therapy-resistant collagen condensation within ASM bundles may facilitate ECM-ASM interactions and contribute to increased internal airways resistance.
Comparison of two twice-daily doses of budesonide/formoterol maintenance and reliever therapy
Authors: Aubier M. , Buhl R. , Ekström T. , Ostinelli J. , van Schayck C.P. , Selroos O. , Haughney J.
Published: July 2010

The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose.

A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting β2-agonist were randomised to budesonide/formoterol 160/4.5 μg, one (1×2) or two (2×2) inhalationsb.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation.

In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2×2versus1×2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2×2. The mean daily ICS doses were 737 and 463 μg in the 2×2 and 1×2 groups, respectively.

In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2×2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.
Vitamin D status and longitudinal lung function decline in the Lung Health Study
Authors: Kunisaki K.M. , Niewoehner D.E. , Singh R.J. , Connett J.E.
Published: July 2010

Low blood vitamin D levels have been postulated to be a risk factor for worse lung function, based largely on cross-sectional data. We sought to use longitudinal data to test the hypothesis that baseline plasma 25-hydroxyvitamin D (25(OH)D) is lower in subjects with more rapid lung function decline, compared to those with slow lung function decline.

We conducted a nested, matched case–control study in the Lung Health Study 3 cohort. Cases and controls were continuous smokers with rapid and slow lung function decline, respectively, over ∼6 yrs of follow-up. We compared baseline 25(OH)D levels between cases and controls, matching date of phlebotomy and clinical centre.

Among 196 subjects, despite rapid and slow decliners experiencing strikingly and significantly different rates of decline of forced expiratory volume in 1 s (-152versus-0.3 mL·yr−1; p<0.001), there was no significant difference in baseline 25(OH)D levels (25.0versus25.9 ng·mL−1; p = 0.54). There was a high prevalence of vitamin D insufficiency (35%) and deficiency (31%); only 4% had a normal 25(OH)D level in the winter.

Although vitamin D insufficiency and deficiency are common among continuous smokers with established mild-to-moderate chronic obstructive pulmonary disease, baseline 25(OH)D levels are not predictive of subsequent lung function decline.
Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome
Authors: Song J.W. , Hong S-B. , Lim C-M. , Koh Y. , Kim D.S.
Published: July 2010

Although acute exacerbation of idiopathic pulmonary fibrosis (IPF) has become well recognised, the reported incidence and outcomes are highly variable, and risk factors are unknown. The aim of this study was to estimate the incidence, risk factors and impact of acute exacerbations, and other known causes of rapid deterioration.

This was a retrospective review of 461 patients with IPF (269 cases were biopsy-proven).

The median follow-up period was 22.9 months. Rapid deterioration requiring hospitalisation occurred in 163 (35.4%) patients, with multiple episodes in 42 patients. Acute exacerbation was the most frequent cause (55.2%), followed by infection. The 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low forced vital capacity (FVC) were significant risk factors. The in-hospital mortality rate was 50.0%, and the 1- and 5-yr survival rates from the initial diagnosis were 56.2 and 18.4%, respectively. Acute exacerbation was a significant predictor of poor survival after the initial diagnosis, along with increased age, low FVC and diffusing capacity of the lung for carbon monoxide, and steroid use with or without cytotoxic therapy.

1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low FVC were risk factors. Acute exacerbation had a serious impact on the overall survival of the patients with IPF.
Particle size matters: diagnostics and treatment of small airways involvement in asthma
Authors: Cohen J. , Postma D.S. , Douma W.R. , Vonk J.M. , De Boer A.H. , ten Hacken N.H.T.
Published: July 2010

Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (ICS) ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed.

After a 4-week run-in period using open-label fluticasone (100 μgb.i.d.), 37 mild-to-moderate asthmatics underwent provocations with standard-size (3.7 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μgs.i.d.) or fluticasone (100 μgb.i.d.) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation.

Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV1) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV1(PC20) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC20by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not.Conversely,fluticasone improved large-particle AMP PC20significantly (1.32 DD; p = 0.03), whereas ciclesonide did not.

Small-particle AMP provocation appears to be a promising tool to assess changes in small airway inflammation. Future adjustments are necessary taking into account the very small particle size used, with large exhaled fractions. In asthmatics reaching a PC20with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.
Global transcriptional profiling of Burkholderia pseudomallei under salt stress reveals differential effects on the Bsa type III secretion system
Authors: Pumirat Pornpan , Cuccui Jon , Stabler Richard A , Stevens Joanne M , Muangsombut Veerachat , Singsuksawat Ekapot , Stevens Mark P , Wren Brendan W , Korbsrisate Sunee
Published: July 2010

Background

Burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the Northeast of Thailand, where saline soil and water are prevalent. Moreover, recent reports indicate a potential pathogenic role for B. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (NaCl) concentration in airway surface liquid has been proposed. These observations raise the possibility that high salinity may represent a favorable niche for B. pseudomallei. We therefore investigated the global transcriptional response of B. pseudomallei to increased salinity using microarray analysis.

Results

Transcriptome analysis of B. pseudomallei under salt stress revealed several genes significantly up-regulated in the presence of 320 mM NaCl including genes associated with the bsa-derived Type III secretion system (T3SS). Microarray data were verified by reverse transcriptase-polymerase chain reactions (RT-PCR). Western blot analysis confirmed the increased expression and secretion of the invasion-associated type III secreted proteins BipD and BopE in B. pseudomallei cultures at 170 and 320 mM NaCl relative to salt-free medium. Furthermore, salt-treated B. pseudomallei exhibited greater invasion efficiency into the lung epithelial cell line A549 in a manner partly dependent on a functional Bsa system.

Conclusions

B. pseudomallei responds to salt stress by modulating the transcription of a relatively small set of genes, among which is the bsa locus associated with invasion and virulence. Expression and secretion of Bsa-secreted proteins was elevated in the presence of exogenous salt and the invasion efficiency was enhanced. Our data indicate that salinity has the potential to influence the virulence of B. pseudomallei.
Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer
Authors: Cocco Emiliano , Casagrande Francesca , Bellone Stefania , Richter Christine E , Bellone Marta , Todeschini Paola , Holmberg Jennie C , Fu Han Hsuan , Montagna Michele K , Mor Gil , Schwartz Peter E , Arin-Silasi Dan , Azoudi Masoud , Rutherford Thomas J , Abu-Khalaf Maysa , Pecorelli Sergio , Santin Alessandro D
Published: July 2010

Background

Development of innovative, effective therapies against recurrent/chemotherapy-resistant ovarian cancer remains a high priority. Using high-throughput technologies to analyze genetic fingerprints of ovarian cancer, we have discovered extremely high expression of the genes encoding the proteins claudin-3 and claudin-4.

Methods

Because claudin-3 and -4 are the epithelial receptors for Clostridium perfringens enterotoxin (CPE), and are sufficient to mediate CPE binding, in this study we evaluated the in vitro and in vivo bioactivity of the carboxy-terminal fragment of CPE (i.e., CPE290-319 binding peptide) as a carrier for tumor imaging agents and intracellular delivery of therapeutic drugs. Claudin-3 and -4 expression was examined with rt-PCR and flow cytometry in multiple primary ovarian carcinoma cell lines. Cell binding assays were used to assess the accuracy and specificity of the CPE peptide in vitro against primary chemotherapy-resistant ovarian carcinoma cell lines. Confocal microscopy and biodistribution assays were performed to evaluate the localization and uptake of the FITC-conjugated CPE peptide in established tumor tissue.

Results

Using a FITC-conjugated CPE peptide we show specific in vitro and in vivo binding to multiple primary chemotherapy resistant ovarian cancer cell lines. Bio-distribution studies in SCID mice harboring clinically relevant animal models of chemotherapy resistant ovarian carcinoma showed higher uptake of the peptide in tumor cells than in normal organs. Imunofluorescence was detectable within discrete accumulations (i.e., tumor spheroids) or even single chemotherapy resistant ovarian cancer cells floating in the ascites of xenografted animals while a time-dependent internalization of the FITC-conjugated CPE peptide was consistently noted in chemotherapy-resistant ovarian tumor cells by confocal microscopy.

Conclusions

Based on the high levels of claudin-3 and -4 expression in chemotherapy-resistant ovarian cancer and other highly aggressive human epithelial tumors including breast, prostate and pancreatic cancers, CPE peptide holds promise as a lead peptide for the development of new diagnostic tracers or alternative anticancer agents.
Cyclin H expression is increased in GIST with very-highrisk of malignancy
Authors: Dorn Julian , Spatz Hanno , Schmieder Michael , Barth Thomas FE , Blatz Annette , Henne-Bruns Doris , Knippschild Uwe , Kramer Klaus
Published: July 2010

Background

Risk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R0resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST.

Methods

In order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed.

Results

Of ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p ≤ 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification.

Conclusion

Our data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.