bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Value of Prior Injury on Career in Professional American Football is Affected by Player Position
Authors: Brophy Robert H. , Lyman Stephen , Chehab Eric L. , Barnes Ronnie P. , Rodeo Scott A. , Warren Russell F.
Published: February 2009

Background

The National Football League holds an annual combine where individual teams evaluate college football players likely to be drafted for physical skills, review players’ medical history and imaging studies, and perform a physical examination.

Purpose

The purpose of this study was to test the effect of specific diagnoses and surgical procedures on the likelihood of playing and length of career in the league by position.

Study Design

Cohort study; Level of evidence, 3.

Methods

A database for all players reviewed at the annual National Football League Combine by the medical staff of 1 National Football League team from 1987 to 2000 was created, including each player's orthopaedic rating, diagnoses, surgical procedures, number of games played, and number of seasons played in the National Football League. Athletes were grouped by position as follows: offensive backfield, offensive receiver, offensive line, quarterback, tight end, defensive line, defensive secondary, linebacker, and kicker. The percentage of athletes who played in the National Football League was calculated by position for each specific diagnosis and surgery.

Results

The effect of injury on the likelihood of playing in the league varied by position. Anterior cruciate ligament injury significantly lowered the likelihood of playing in the league for defensive linemen ( P = .03) and linebackers ( P = .04). Meniscal injury significantly reduced the probability of playing ( P < .05) and length of career ( P = .002) for athletes in the defensive secondary. Shoulder instability had a significant effect on playing in the league for offensive ( P = .03) and defensive linemen ( P = .02), and shortened the length of career for defensive linemen ( P = .016). Spondylolisthesis did not significantly reduce the chance of playing in the league for any position, while a history of spondylolysis had a significant effect for running backs ( P = .01). Miscellaneous injuries (eg. acromioclavicular joint, knee medial collateral ligament, carpal fractures) had isolated position-specific effects.

Conclusion

The significant injuries and diagnoses appear congruent with the position-specific demands placed on the athletes. This information is useful to physicians and athletic trainers caring for college football athletes as well as those assessing these athletes at the National Football League Combine.
Layered Landscape
Authors: Morel-EdnieBrown Felicity
Published: February 2009

This study focuses on a very small area of land that forms part of the northern central business district of Perth in Western Australia. In investigating this microscale of human occupation, the use of Geographic Information System (GIS) was a research tool to investigate traditional historical sources not commonly thought of by historians as spatial. Changes, rediscovered through the agency of GIS, showed that the northern part of the townscape was intimately defined and cast in response to its swampland topography.
A Review of Observational Pain Scales in Nonverbal Elderly With Cognitive Impairments
Authors: Juyoung Park  , Castellanos-Brown Karen , Belcher John
Published: February 2009

Objective: Pain assessment for nonverbal older adults with cognitive impairments or dementia presents many challenges, and it is important to determine which scales are most useful in assessing pain among this population. Method: In this review 11 observational scales for assessment of pain in older adults with dementia or cognitive impairments are evaluated in four areas: pain indicators, reliability, validity, and clinical utility of the measure. Results: Results indicate that various scales are available for assessing pain in cognitively impaired or demented older adults who are unable to report their pain, but future research should focus on further psychometric evaluations. Conclusions: Implications include that social workers should be trained as raters of pain assessment methods.
Ladies Without Lamps: Nurses in Bangladesh
Authors: Zaman Shahaduz
Published: February 2009

In this article, I explore the experiences and concerns of Bangladeshi nurses. I have based this on a larger ethnographic study that was conducted in a ward of a government teaching hospital in Bangladesh. The study shows how the values and norms of Bangladeshi society have shaped the life of Bangladeshi nurses, that they do scarcely any nursing work, and that they suffer from various negative social images. I argue, through this article, that the role, image, and concerns of Bangladeshi nurses have changed dramatically from the ideal image of nursing, and are dissimilar from the ways nursing is practiced in many other parts of the world.
Where Is the Jury?
Authors: Donaldson Lex
Published: February 2009

A key idea in social science is that the work by any one scholar should be carefully evaluated by other scholars, to form an impartial, authoritative, collective judgment. Thus, peers are supposed to act as a jury. However, often there seems to be no effective jury in organizational science. There is an absence of extended debate in which the details of theories and research are assessed and then a definitive, consensual judgment made. Colleagues often fail to adequately consider others' work, in part because of disinclination to entertain rival theories. Again, specialization means expert peer scrutiny is frequently missing. Conferences such as Academy of Management meetings typically fail to provide in-depth discussion or scrutiny. I illustrate some of the factors that militate against proper scientific evaluation with candid cases from my own research experience.
Intergovernmental Revenue Estimation
Authors: Ványolós István
Published: February 2009

This study develops a model of school budget decision making and examines the nature of state aid estimation. Revenue estimation can be divided into three distinct components: strategy-driven difference, uncertainty-triggered difference, and true error term. Underestimation of state aid revenues is the dominant budgetary behavior, but a significant number of districts end up with undesired overestimation. Overestimation is more prevalent among high aid dependent, rural, and urban districts. Institutional constraints, such as local budget vote, tend to reduce the size of state aid estimation difference. The uncertainty-triggered difference tends to increase as a response to compounded negative signals (low levels of Governor's proposal on state aid and late state budgets). Although there is evidence that state aid estimation differences ultimately end up in the fund balance, this study could not confirm that lower levels of prior year fund balances would trigger districts into a more aggressive underestimation of state aid.
How to Balance the Load on Heterogeneous Clusters
Authors: Beltrán Marta , Guzmán Antonio
Published: February 2009

The problem of computing a large set of different tasks on a set of heterogeneous resources connected by a network is very common nowadays in very different environments and load balancing is indispensable for achieving high performance and high throughput in systems such as clusters. Cluster heterogeneity increases the difficulty of balancing the load across the system nodes and, although the relationship between heterogeneity and load balancing is difficult to describe analytically, in this paper different models and performance metrics are proposed to describe heterogeneous cluster behavior and to perform an exhaustive analysis of the effects of heterogeneity on load balancing algorithm performance. This analysis allows us to propose efficient solutions capable of dealing with heterogeneity for all the load balancing algorithm stages. Furthermore, a load balancing algorithm has been implemented following these solutions to demonstrate, with experimental results, its efficiency on real heterogeneous clusters.
Solicited audio diaries in longitudinal narrative research: a view from inside
Authors: Monrouxe Lynn V.
Published: February 2009

The use of solicited audio diaries in longitudinal qualitative enquiry is rare. Moreover, an understanding of the unique insights that these diaries might give the qualitative researcher has largely been absent in our consideration of appropriate methods for data collection. This article aims to address this deficit by providing a critical reflection on the use of solicited audio diaries in longitudinal narrative research from practical, theoretical and analytical perspectives. The data is drawn from a longitudinal study investigating medical students' professional identity formation. In an attempt to reach the broadest audience, both structural aspects and communicative elements of talk within the data are considered alongside ethical issues and emotional work that the longitudinal audio-diary researcher might encounter. In addition to presenting extracts from a variety of diary entries, a single event narrative is presented in full, alongside an analysis, in order to demonstrate the powerful utility of this underused method.
Valence Image and the Standardisation of Democratic Political Leadership
Authors: Barisione Mauro
Published: February 2009

The principles of selection of national candidates and contenders for political leadership are becoming increasingly standardised in Western contemporary democracies, which have been affected by two widespread processes: first, the growth of mass political communication via the electronic media; and second, the increasing deficit of perceived legitimacy of traditional representative institutions. After analysing such processes, this article draws attention to their standardising effects on the images of contemporary leaders. These are analysed in terms of three main elements: image traits, image types, and `vision'. Presenting and developing the notion of `valence image'as the most important dimension of a political leader's image, the article posits that two sets of `valence' image traits (`effectiveness' and `trustworthiness'), four image ideal-types (the `Outsider', the `Strong Leader', the `Everyday Man', the `Post-ideological'), as well as the presence of a consensual `vision' of the country have become the essential and standard prerequisites for access to contemporary political leadership.
Evidence and liberty
Authors: Sherman Lawrence W.
Published: February 2009

Evidence and liberty are two great ideas in British history. One consequence of both ideas is experimental criminology, which applies research designs developed in Britain to matters of liberty affecting the entire world. The promise of experimental criminology is to generate better evidence about how to increase liberty. The crucial challenge to experimental criminology is the means by which research results, even when accepted as true, may be translated into widespread practice. Two models for applying experimental research are possible. One is `bottom—up discretion', in which crime victims, police, judges and probation officers and others take experimental results into account when making their decisions one case at a time. Another model is `top—down guidance', in which either Ministers or an independent evidence-assessment agency like `NICE'—the National Institute of Health and Clinical Excellence—appoint committees of practitioners and researchers to develop succinct operational guidance based upon systematic reviews of experimental evidence. Bottom—up discretion will grow steadily from the sheer persistence of criminologists and practitioners doing experiments. Liberty could be advanced much faster by top—down guidance, however, if government chose to invest in `prospective meta-analysis' a method of multi-site randomized trials that would assess generalizability of policy effects as well as their magnitude and cost-effectiveness.
Criminal thinking and self-control among drug users in court mandated treatment
Authors: Packer Greg , Best David , Day Ed , Wood Kelly
Published: February 2009

This article aims to explore the relationship between self-control and criminal thinking in a population of drug using offenders attending a court mandated treatment programme, and how this relates to recent offending and substance use. Fifty drug using offenders attending a Birmingham Drug Intervention Programme clinic under the terms of a Drug Rehabilitation Requirement (DRR) completed standardized measures of self-control and criminal thinking. Associations were found between both self-control and criminal thinking and drug use and offending. A strong association was found between low self-control and high criminal thinking. Lower levels of self-control were associated with younger age, and there was some evidence of a link between younger age and higher criminal thinking. The links between drug use and crime are more complex than could be explained by either the self-control model of crime or criminal thinking alone, although the current findings suggest a mediating role for age and indications that drugs—crime linkage is mediated by patterns of substance use and offending.
Tensile properties of jute fibres
Authors: Virk A. S. , Hall W. , Summerscales J.
Published: February 2009

One hundred tensile tests were undertaken at each of five distinct fibre lengths (6, 10, 20, 30 and 50 mm) on a single batch of jute fibres from South Asia. The Young's moduli were found to be independent of length. The ultimate stress (fracture strength) and fracture strains were found to decrease with increasing fibre length. The variation in mechanical properties at each fibre length was characterised using Weibull statistics based on a maximum likelihood estimate; referred to as point estimates. Two empirical based models (a linear and a natural logarithmic interpolation model) have been developed to estimate the fracture properties at any length between 6 and 50 mm. These two interpolation models were also developed based on maximum likelihood estimates. The point estimates were used to benchmark the performance of the two models. The natural logarithmic model was found to be superior to the linear model.
Cytokine changes during rituximab therapy in HIV-associated multicentric Castleman disease
Authors: Bower Mark , Veraitch Ophelia , Szydlo Richard , Charles Peter , Kelleher Peter , Gazzard Brian , Nelson Mark , Stebbing Justin
Published: February 2009

Recent data highlight the importance of inflammatory markers during human immunodeficiency virus type 1 (HIV) infection. HIV-associated multicentric Castleman disease (HIV-MCD) presents with systemic symptoms attributed to cytokine disarray, and we have previously shown that the use of the anti-CD20 monoclonal antibody rituximab induces clinical remissions. Before and during successful rituximab therapy, 15 plasma cytokines were measured as were adaptive (CD4, CD8, CD19) and innate (CD16/56) immune cell populations and HIV-1 viral loads. A significant reduction from baseline of the CD19 B-cell count, consistent with rituximab's mechanism of action, was observed. Markedly elevated cytokine levels were observed before rituximab therapy, and a reduction from baseline values with rituximab therapy was observed for interleukin (IL)-5, IL-6, and IL-10. Therapies that reduce the inflammatory cytokine response are likely to be successful in a range of diseases, including HIV-MCD, and in the future may be used to guide therapeutic strategies.
Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study
Authors: Ställberg Björn , Selroos Olof , Vogelmeier Claus , Andersson Eva , Ekström Tommy , Larsson Kjell
Published: February 2009

Background

Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.

Methods

This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.

A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined.

Results

Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.

Conclusion

High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.

Clinical trial registration

NCT00259779
Structural studies of the Enterococcus faecalis SufU [Fe-S] cluster protein
Authors: Riboldi Gustavo P , Verli Hugo , Frazzon Jeverson
Published: February 2009

Background

Iron-sulfur clusters are ubiquitous and evolutionarily ancient inorganic prosthetic groups, the biosynthesis of which depends on complex protein machineries. Three distinct assembly systems involved in the maturation of cellular Fe-S proteins have been determined, designated the NIF, ISC and SUF systems. Although well described in several organisms, these machineries are poorly understood in Gram-positive bacteria. Within the Firmicutes phylum, the Enterococcus spp. genus have recently assumed importance in clinical microbiology being considered as emerging pathogens for humans, wherein Enterococcus faecalis represents the major species associated with nosocomial infections. The aim of this study was to carry out a phylogenetic analysis in Enterococcus faecalis V583 and a structural and conformational characterisation of it SufU protein.

Results

BLAST searches of the Enterococcus genome revealed a series of genes with sequence similarity to the Escherichia coli SUF machinery of [Fe-S] cluster biosynthesis, namely sufB, sufC, sufD and SufS. In addition, the E. coli IscU ortholog SufU was found to be the scaffold protein of Enterococcus spp., containing all features considered essential for its biological activity, including conserved amino acid residues involved in substrate and/or co-factor binding (Cys50,76,138 and Asp52) and, phylogenetic analyses showed a close relationship with orthologues from other Gram-positive bacteria. Molecular dynamics for structural determinations and molecular modeling using E. faecalis SufU primary sequence protein over the PDB:1su0 crystallographic model from Streptococcus pyogenes were carried out with a subsequent 50 ns molecular dynamic trajectory. This presented a stable model, showing secondary structure modifications near the active site and conserved cysteine residues. Molecular modeling using Haemophilus influenzae IscU primary sequence over the PDB:1su0 crystal followed by a MD trajectory was performed to analyse differences in the C-terminus region of Gram-positive SufU and Gram-negative orthologous proteins, in which several modifications in secondary structure were observed.

Conclusion

The data describe the identification of the SUF machinery for [Fe-S] cluster biosynthesis present in the Firmicutes genome, showing conserved sufB, sufC, sufD and sufS genes and the presence of the sufU gene coding for scaffold protein, instead of sufA; neither sufE nor sufR are present. Primary sequences and structural analysis of the SufU protein demonstrated its structural-like pattern to the scaffold protein IscU nearby on the ISC machinery. E. faecalis SufU molecular modeling showed high flexibility over the active site regions, and demonstrated the existence of a specific region in Firmicutes denoting the G ram p ositive r egion (GPR), suggested as a possible candidate for interaction with other factors and/or regulators.
Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation
Authors: Choe Jonathan M , Bakthavatsalam Deenadayalan , Phillips Jonathan E , Gomer Richard H
Published: February 2009

Background

Dictyostelium cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA.

Results

We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 μg/ml near a stationary cell density. When added to wild-type or aprA
- cells, recombinant AprA (rAprA) significantly slows proliferation at 0.1 μg/ml and higher concentrations. From 4 to 64 μg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating aprA
- cells show saturable binding of rAprA to 92,000 ± 11,000 cell-surface receptors with a K

D
of 0.03 ± 0.02 μg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to aprA
- cells with a K

i
of 0.03 μg/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA.

Conclusion

Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a CfaD receptor, and activation of both receptors is required to slow proliferation. We previously found that crlA
- cells are sensitive to CfaD. Combined with the results presented here, this suggests that CrlA is not the AprA or CfaD receptor, and may be the receptor for an unknown third factor that is required for AprA and CfaD activity.
The effects of whole mushrooms during inflammation
Authors: Yu Sanhong , Weaver Veronika , Martin Keith , Cantorna Margherita T
Published: February 2009

Background

Consumption of edible mushrooms has been suggested to improve health. A number of isolated mushroom constituents have been shown to modulate immunity. Five commonly consumed edible mushrooms were tested to determine whether whole mushrooms stimulate the immune system in vitro and in vivo.

Results

The white button (WB) extracts readily stimulated macrophage production of TNF-α. The crimini, maitake, oyster and shiitake extracts also stimulated TNF-α production in macrophage but the levels were lower than from WB stimulation. Primary cultures of murine macrophage and ovalbumin (OVA) specific T cells showed that whole mushroom extracts alone had no effect on cytokine production but co-stimulation with either lipopolysacharide or OVA (respectively) induced TNF-α, IFN-γ, and IL-1β while decreasing IL-10. Feeding mice diets that contained 2% WB mushrooms for 4 weeks had no effect on the ex vivo immune responsiveness or associated toxicity (changes in weight or pathology of liver, kidney and gastrointestinal tract). Dextran sodium sulfate (DSS) stimulation of mice that were fed 1% WB mushrooms were protected from DSS induced weight loss. In addition, 2% WB feeding protected the mice from transient DSS induced colonic injury. The TNF-α response in the colon and serum of the DSS challenged and 2% WB fed mice was higher than controls.

Conclusion

The data support a model whereby edible mushrooms regulate immunity in vitro. The in vivo effects of edible mushrooms required a challenge with DSS to detect small changes in TNF-α and transient protection from colonic injury. There are modest effects of in vivo consumption of edible mushrooms on induced inflammatory responses. The result is not surprising since it would certainly be harmful to strongly induce or suppress immune function following ingestion of a commonly consumed food.
Self-care coping strategies in people with diabetes: a qualitative exploratory study
Authors: Collins Margaret M , Bradley Colin P , O'Sullivan Tony , Perry Ivan J
Published: February 2009

Background

The management of diabetes self-care is largely the responsibility of the patient. With more emphasis on the prevention of complications, adherence to diabetes self-care regimens can be difficult. Diabetes self-care requires the patient to make many dietary and lifestyle changes. This study will explore patient perceptions of diabetes self-care, with particular reference to the burden of self-care and coping strategies among patients.

Methods

A maximum variation sample of 17 patients was selected from GP practices and diabetes clinics in Ireland to include patients with types 1 and 2 diabetes, various self-care regimens, and a range of diabetes complications. Data were collected by in-depth interviews; which were tape-recorded and transcribed. The transcripts were analysed using open and axial coding procedures to identify main categories, and were reviewed by an independent corroborator. Discussion of the results is made in the theoretical context of the health belief, health value, self-efficacy, and locus of control frameworks.

Results

Patients' perceptions of their self-care varied on a spectrum, displaying differences in self-care responsibilities such as competence with dietary planning, testing blood sugar and regular exercise. Three patient types could be distinguished, which were labeled: "proactive manager," a patient who independently monitors blood glucose and adjusts his/her self-care regime to maintain metabolic control; "passive follower," a patient who follows his/her prescribed self-care regime, but does not react autonomously to changes in metabolic control; and "nonconformist," a patient who does not follow most of his/her prescribed self-care regimen.

Conclusion

Patients have different diabetes self-care coping strategies which are influenced by their self-care health value and consequently may affect their diet and exercise choices, frequency of blood glucose monitoring, and compliance with prescribed medication regimens. Particular attention should be paid to the patient's self-care coping strategy, and self-care protocols should be tailored to complement the different patient types.
Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy
Authors: Burkhardt Klaus , Schwarz Sonja , Pan Chengrui , Stelter Felix , Kotliar Konstantin , Von Eynatten Maxilian , Sollinger Daniel , Lanzl Ines , Heemann Uwe , Baumann Marcus
Published: February 2009

Background

Inflammation contributes to cardiovascular complications in type 2 diabetes, which are often characterized by microvascular alterations. We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy.

Methods

MRP8/14 was measured in 43 patients with type 2 diabetes and nephropathy. Additionally, the inflammatory markers Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were quantified. To detect microvascular alterations proteinuria and retinal vessel caliber were used as classical and novel marker, respectively. Proteinuria was quantified by protein-creatinine ratio (PCR); retinal vessel caliber was quantified after retina photography on digitalized retina pictures.

Results

MRP8/14 was positively associated with inflammation (r = 0.57), proteinuria (r = 0.40) and retinal arterial caliber (r = 0.48). Type 2 diabetic patients with MRP8/14 values above the median of 5.8 μg/ml demonstrated higher proteinuria and larger retinal artery caliber than patients with MRP8/14 values below the median (logPCR: -0.51 ± 0.52 versus -0.96 ± 0.46, P < 0.01; retinal artery lumen (μm): 178.3 ± 14.1 versus 162.7 ± 14.9 P < 0.01). Both groups did not differ with regard to metabolic factors and blood pressure. MRP8/14 was an independent predictor of retinal artery caliber in multivariate stepwise regression analysis (β = 0.607) and was positively associated with IL-6 (r = 0.57, P < 0.001) and TNF-α (r = 0.36, P < 0.05).

Conclusion

MRP8/14 – a marker for transendothelial migration – describes not only the state of inflammation in diabetic nephropathy, but additionally the degree of microvascular alterations in the glomerular and retinal bed. Therefore, MRP8/14 may be a potentially selective novel biomarker for microcirculatory defects in diabetic nephropathy.
The proliferative human monocyte subpopulation contains osteoclast precursors
Authors: Lari Roya , Kitchener Peter D , Hamilton John A
Published: February 2009

Introduction

Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors.

Methods

Human peripheral blood monocytes were sorted based upon their degree of proliferation and cultured in macrophage colony-stimulating factor (M-CSF or CSF-1) and receptor activator of nuclear factor-kappa-B ligand (RANKL).

Results

The monocyte subpopulation that is capable of proliferation gave rise to significantly more multinucleated, bone-resorbing osteoclasts than the bulk of the monocytes.

Conclusions

Human peripheral blood osteoclast precursors reside in the proliferative monocyte subpopulation.
Imaging salt bodies using explicit migration operators offshore Norway
Authors: Arntsen Børge , Gerea Constantin , Røsten Tage
Published: February 2009

We have tested the performance of 3D shot-profile depth migration using explicit migration operators on a real 3D marine data set. The data were acquired offshore Norway in an area with a complex subsurface containing large salt bodies. We compared shot-profile migration using explicit migration operators with conventional Kirchhoff migration, split-step Fourier migration, and common-azimuth by generalized screen propagator (GSP) migration in terms of quality and computational cost. Image quality produced by the explicit migration operator approach is slightly better than with split-step Fourier migration and clearly better than in common-azimuth by GSP and Kirchhoff migrations. The main differences are fewer artifacts and better-suppressed noise within the salt bodies. Kirchhoff migration shows considerable artifacts (migration smiles) within and close to the salt bodies, which are not present in images produced by the other three wave-equation methods. Expressions for computational cost were developed for all four migration algorithms in terms of frequency content and acquisition parameters. For comparable frequency content, migration cost using explicit operators is four times the cost of the split-step Fourier method, up to 260 times the cost of common-azimuth by GSP migration, and 25 times the cost of Kirchhoff migration. Our results show that in terms of image quality, shot-profile migration using explicit migration operators is well suited for imaging in areas with complex geology and significant velocity changes. However, computational cost of the method is high and makes it less attractive in terms of efficiency.
Ray tracing by simulated annealing: Bending method
Authors: Bóna Andrej , Slawinski Michael A. , Smith Peter
Published: February 2009

We propose a new ray-tracing method based on the concept of simulated annealing. Using this method, we find rays between fixed sources and receivers that render traveltime globally minimal. With our method, we are able to construct rays and their associated traveltimes to satisfactory precision in complex media. Furthermore, our algorithm can be modified to calculate rays of locally minimum traveltime, such as reflected rays, by constraining the ray to pass through a set of points that we are free to specify.
Cooperative Trial CWS-91 for Localized Soft Tissue Sarcoma in Children, Adolescents, and Young Adults
Authors: Dantonello Tobias M. , Int-Veen Christoph , Harms Dieter , Leuschner Ivo , Schmidt Bernhard F. , Herbst Manfred , Juergens Heribert , Scheel-Walter Hans-Gerhard , Bielack Stefan S. , Klingebiel Thomas , Dickerhoff Roswitha , Kirsch Sylvia , Brecht Ines , Schmelzle Rainer , Greulich Michael , Gadner Helmut , Greiner Jeanette , Marky Ildiko , Treuner Joern , Koscielniak Ewa
Published: February 2009

Purpose

To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting.

Patients and Methods

Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy.

Results

At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% ± 4% and 73% ± 4%, respectively (all survival rates in this abstract are calculated and displayed with ±95% CI). EFS/OS rates by histology were 60% ± 5%/72% ± 5% in rhabdomyosarcoma, 62% ± 10%/69% ± 10% for Ewing tumors of soft tissues, 84% ± 12%/90% ± 10% for synovial sarcoma, and 67% ± 38%/83% ± 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% ± 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% ± 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis.

Conclusion

Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.
Trimodality Therapy With Induction Chemotherapy Followed by Extrapleural Pneumonectomy and Adjuvant High-Dose Hemithoracic Radiation for Malignant Pleural Mesothelioma
Authors: de Perrot Marc , Feld Ronald , Cho B.C. John , Bezjak Andrea , Anraku Masaki , Burkes Ronald , Roberts Heidi , Tsao Ming S. , Leighl Natasha , Keshavjee Shaf , Johnston Michael R.
Published: February 2009

Purpose

Malignant pleural mesothelioma (MPM) remains associated with poor outcome. We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy (EPP) and adjuvant high-dose (50 to 60 Gy) hemithoracic radiation therapy for MPM.

Patients and Methods

We conducted a retrospective review of all patients prospectively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution.

Results

A total of 60 patients were suitable candidates. Histology was epithelioid (n = 44) or biphasic (n = 16). Chemotherapy regimens included cisplatin/vinorelbine (n = 26), cisplatin/pemetrexed (n = 24), cisplatin/raltitrexed (n = 6), or cisplatin/gemcitabine (n = 4). EPP was performed in 45 patients, and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients. Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival (median survival of 59 months v ≤ 14 months in the remaining patients, P = .0003). The type of induction chemotherapy had no significant impact on survival. Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy. After completion of the protocol, the 5-year disease-free survival was 53% for patients with N0 disease, reaching 75% in patients with ypT1-2N0 and 45% in patients with ypT3-4N0.

Conclusion

This large, single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol. The results are encouraging for patients with N0 disease. However, N2 disease remains a major factor impacting on survival, despite completion of the entire trimodality regimen.
Phase II Evaluation of Nanoparticle Albumin–Bound Paclitaxel in Platinum-Sensitive Patients With Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer
Authors: Teneriello Michael G. , Tseng Paul C. , Crozier Mark , Encarnacion Carlos , Hancock Kenneth , Messing Mark J. , Boehm Kristi A. , Williams Alicia , Asmar Lina
Published: February 2009

Purpose

Patients with recurrent ovarian, peritoneal, or fallopian tube cancer have limited therapeutic options. There are no reports of nanoparticle albumin–bound paclitaxel (nab-paclitaxel) in patients with recurrent platinum-sensitive disease. We report efficacy and toxicity with nab-paclitaxel in this group.

Patients and Methods

Forty-seven patients enrolled (44 assessable patients). Main inclusion criteria were histologically or cytologically confirmed epithelial cancer of the ovary, fallopian tube, or peritoneum (any stage, grade 2 to 3 if stage I) and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or elevated CA-125 (> 70 U/mL) in patients without measurable disease. Patients received nab-paclitaxel 260 mg/m2 administered intravenously for 30 minutes on day 1 of a 21-day cycle for six cycles or until disease progression.

Results

Median age was 65.5 years; 76% of patients had stage IIIC or IV disease, 81% had Eastern Cooperative Oncology Group performance status of 0, and 94% had prior surgery. For assessable patients, the objective response rate (ORR) was 64% (15 complete responses [CR] and 13 partial responses [PR] among 44 assessable patients). In patients evaluated with RECIST only, the ORR was 45% (one CR and four PR of 11 patients). In patients with only elevated CA-125, ORR was 82% (seven CRs and two PRs of 11 patients). In patients meeting both RECIST and CA-125 criteria, the ORR was 64% (seven CRs and seven PRs of 22 patients). Median time to response was 1.3 months (range, 0.5 to 4.8 months). Estimated median progression-free survival was 8.5 months. The most frequent grade 3 to 4 treatment-related toxicities were neutropenia (24%) and neuropathy (9%).

Conclusion

Nab-paclitaxel is active in this group of patients with recurrent ovarian, peritoneal, or fallopian tube cancer. The ORR was 64%. Toxicities were manageable. Further studies of nab-paclitaxel in combination with platinum are warranted.
Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Authors: Feldman Darren R. , Baum Michael S. , Ginsberg Michelle S. , Hassoun Hani , Flombaum Carlos D. , Velasco Susanne , Fischer Patricia , Ronnen Ellen , Ishill Nicole , Patil Sujata , Motzer Robert J.
Published: February 2009

Purpose

Both bevacizumab and sunitinib target the vascular endothelial growth factor pathway and demonstrate activity against advanced renal cell carcinoma (RCC). In this phase I study, the maximum-tolerated dose (MTD) and safety of sunitinib in combination with bevacizumab were examined in patients with advanced RCC.

Patients and Methods

Three cohorts of three to six patients were treated with escalated doses of daily oral sunitinib (ie, 25 mg, 37.5 mg, 50 mg) for 4 weeks followed by a 2-week break and with fixed doses of bevacizumab (10 mg/kg) intravenously once every 2 weeks. Dose-limiting toxicities (DLTs) were assessed during the first cycle to determine the MTD, and an expanded cohort was treated to obtain additional safety information.

Results

Of 26 study participants, 25 received treatment at one of three dose levels. Grade 4 hemorrhage, identified as a DLT, occurred in one patient in each of cohorts 2 and 3. The MTD was determined to be sunitinib 50 mg/bevacizumab 10 mg/kg, but chronic therapy at this dose level frequently resulted in grades 3 to 4 hypertension and hematologic and vascular toxicities. Overall, 48% of patients discontinued treatment because of adverse events. One complete and 12 partial responses were observed, which provided an objective response rate of 52%.

Conclusion

In this phase I trial of patients with metastatic RCC, the combination of sunitinib and bevacizumab caused a high degree of hypertension and vascular and hematologic toxicities at the highest dose level. We do not plan to pursue additional study of this regimen at these doses in patients with RCC.
Evaluation of New Platinum-Based Treatment Regimens in Advanced-Stage Ovarian Cancer: A Phase III Trial of the Gynecologic Cancer InterGroup
Authors: Bookman Michael A. , Brady Mark F. , McGuire William P. , Harper Peter G. , Alberts David S. , Friedlander Michael , Colombo Nicoletta , Fowler Jeffrey M. , Argenta Peter A. , De Geest Koen , Mutch David G. , Burger Robert A. , Swart Ann Marie , Trimble Edward L. , Accario-Winslow Chrisann , Roth Lawrence M.
Published: February 2009

Purpose

To determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel.

Patients and Methods

Women with stages III to IV disease were stratified by coordinating center, maximal diameter of residual tumor, and intent for interval cytoreduction and were then randomly assigned among five arms that incorporated gemcitabine, methoxypolyethylene glycosylated liposomal doxorubicin, or topotecan compared with carboplatin and paclitaxel. The primary end point was OS and was determined by pairwise comparison to the reference arm, with a 90% chance of detecting a true hazard ratio of 1.33 that limited type I error to 5% (two-tail) for the four comparisons.

Results

Accrual exceeded 1,200 patients per year. An event-triggered interim analysis occurred after 272 events on the reference arm, and the study closed with 4,312 women enrolled. Arms were well balanced for demographic and prognostic factors, and 79% of patients completed eight cycles of therapy. There were no improvements in either PFS or OS associated with any experimental regimen. Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup.

Conclusion

Compared with standard paclitaxel and carboplatin, addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction. Dual-stage, multiarm, phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm. The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC.
Increasing Rates of Contralateral Prophylactic Mastectomy Among Patients With Ductal Carcinoma In Situ
Authors: Tuttle Todd M. , Jarosek Stephanie , Habermann Elizabeth B. , Arrington Amanda , Abraham Anasooya , Morris Todd J. , Virnig Beth A.
Published: February 2009

Purpose

Some women with unilateral ductal carcinoma in situ (DCIS) undergo contralateral prophylactic mastectomy (CPM) to prevent cancer in the opposite breast. The use and trends of CPM for DCIS in the United States have not previously been reported.

Methods

We used the Surveillance, Epidemiology, and End Results database to analyze the initial treatment (within 6 months) of patients with unilateral DCIS diagnosed from 1998 through 2005. We determined the CPM rate as a proportion of all surgically treated patients and as a proportion of all patients who underwent mastectomy. We compared demographic and tumor variables in women with unilateral DCIS who underwent surgical treatment.

Results

We identified 51,030 patients with DCIS; 2,072 patients chose CPM. The CPM rate was 4.1% for all surgically treated patients and 13.5% for patients undergoing mastectomy. Among all surgically treated patients (including breast-conserving surgery), the CPM rate increased by 148% from 1998 (2.1%) to 2005 (5.2%). Among patients who underwent mastectomy to treat DCIS (excluding patients undergoing breast-conserving surgery), the CPM rate increased by 188% from 1998 (6.4%) to 2005 (18.4%). Young patient age, white race, recent year of diagnosis, and the presence of lobular carcinoma in situ were significantly associated with higher CPM rates among all surgically treated patients and all patients undergoing mastectomy. Large tumor size and higher grade were significantly associated with increased CPM rates among all surgically treated patients but lower CPM rates among patients undergoing mastectomy.

Conclusion

The use of CPM for DCIS in the United States markedly increased from 1998 through 2005.