bluuebunny/crossref_metadata_2025_split huggingface dataset:
Information-theory based surrogate marker evaluation from several randomized clinical trials with continuous true and binary surrogate endpoints
Authors: Pryseley Assam , Tilahun Abel , Alonso Ariel , Molenberghs Geert 
Published: November 2007

Background Surrogate endpoints potentially reduce the duration and/or increase the amount of information available in a study, thereby diminishing patient burden and cost. They may also increase the effectiveness and reliability of research, through beneficial impact on noncompliance and missingness. Purpose In this article, we review the meta-analytic approach of Buyse et al. (2000) and its extension to mixed continuous and binary endpoints by Molenberghs Geys, and Buyse (2001). Methods An information-theoretic alternative, based on Alonso and Molenberghs (2007a) is proposed. The method is evaluated using simulations and application to data from an ophthalmologic trial, with lines of vision lost at 6 months as candidate surrogate endpoints for lines of vision lost at 12 months. The method is implemented as an R function. Results The information-theoretic approach is based on solid theory, easy to apply, and enjoys elegant properties. While the information-theoretic approach appears to be somewhat biased downwards, this is due to fact that it operates at explicitly observed outcomes, without the need for unobserved, latent scales. This is a desirable property. Limitations While easy-to-use and implement, the theoretical foundation of the information-theory approach is more mathematical. It produces some bias for small to moderate trial/center sizes, and hence is recommended primarily for sufficiently large trials. Conclusions Since the meta-analytic framework can be computationally extremely expensive, the information-theoretic approach of Alonso and Molenberghs (2007a) is a viable alternative. For the ophthalmologic case study, the conclusion is that the lines of vision lost at sixth month do have some, but not overwhelming promise as a surrogate endpoint. Clinical Trials 2007; 4: 587—597. http://ctj.sagepub.com
The Veterans Affairs Low Vision Intervention Trial (LOVIT): Design and Methodology
Authors: Stelmack Joan A , Tang X. Charlene , Reda Domenic J. , Moran D'Anna , Rinne Stephen , Mancil Rickilyn M. , Cummings Roger , Mancil Gary , Stroupe Kevin , Ellis Nancy , Massof Robert W. 
Published: November 2007

Background Visual impairment is a major public health problem. Vision rehabilitation programs have the potential to restore independence and improve quality of life for persons with permanent vision loss, and few have been evaluated in randomized controlled trials. Purpose The Veterans Affairs (VA) Low Vision Intervention Trial is a multicenter randomized clinical trial to evaluate the effectiveness of a new outpatient low vision rehabilitation program. Methods 126 patients with moderate and severe vision loss due to macular diseases are randomized to low vision treatment in an outpatient setting or a usual care control group at two VA facilities in Hines, Illinois, and Salisbury, North Carolina. The primary outcome is the change in visual reading ability from baseline to four months measured with the Veterans Affairs Low Vision Visual Functioning Questionnaire-48 (VA LV VFQ-48). Secondary outcomes compare the mean change in visual ability measured with the VA LV VFQ-48 (overall ability, mobility, visual information processing, visual motor skills) for the treatment and control groups. Costs and cost effectiveness of outpatient treatment are evaluated. Results The low vision rehabilitation setting, use of a waiting list control group to address ethical issues, development of the treatment protocol, development of a vision function questionnaire for patients to self-report the difficulty they experience performing daily activities, and the use of Rasch analysis to develop and estimate this outcome measure are described. Limitations If the new low vision rehabilitation program is proven effective, studies will be needed to determine which of the multiple aspects of the intervention are necessary and sufficient. Conclusions The challenges of conducting clinical trials in a rehabilitation setting and use of a waiting list (deferred treatment) control group extend beyond LOVIT. The design and methods of LOVIT may be applicable to other trials of rehabilitation services and to outcomes for which reliable and valid measurement tools must be developed. Clinical Trials 2007; 4: 650—660. http://ctj.sagepub.com
In situ analysis of cross-hybridisation on microarrays and the inference of expression correlation
Authors: Casneuf Tineke , Van de Peer Yves , Huber Wolfgang 
Published: November 2007

Abstract

Background
Microarray co-expression signatures are an important tool for studying gene function and relations between genes. In addition to genuine biological co-expression, correlated signals can result from technical deficiencies like hybridization of reporters with off-target transcripts. An approach that is able to distinguish these factors permits the detection of more biologically relevant co-expression signatures.

Results
We demonstrate a positive relation between off-target reporter alignment strength and expression correlation in data from oligonucleotide genechips. Furthermore, we describe a method that allows the identification, from their expression data, of individual probe sets affected by off-target hybridization.

Conclusion
The effects of off-target hybridization on expression correlation coefficients can be substantial, and can be alleviated by more accurate mapping between microarray reporters and the target transcriptome. We recommend attention to the mapping for any microarray analysis of gene expression patterns.
Effect of spatial resolution on cluster detection: a simulation study
Authors: Ozonoff Al , Jeffery Caroline , Manjourides Justin , White Laura Forsberg , Pagano Marcello 
Published: November 2007

AbstractBackgroundAggregation of spatial data is intended to protect privacy, but some effects of aggregation on spatial methods have not yet been quantified.MethodsWe generated 3,000 spatial data sets and evaluated power of detection at 12 different levels of aggregation using the spatial scan statistic implemented in SaTScan v6.0.ResultsPower to detect clusters decreased from nearly 100% when using exact locations to roughly 40% at the coarsest level of spatial resolution.ConclusionAggregation has the potential for obfuscation.
Localization of HIV-1 Vpr to the nuclear envelope: Impact on Vpr functions and virus replication in macrophages
Authors: Jacquot Guillaume , Le Rouzic Erwann , David Annie , Mazzolini Julie , Bouchet Jérôme , Bouaziz Serge , Niedergang Florence , Pancino Gianfranco , Benichou Serge 
Published: November 2007

Abstract

Background
HIV-1 Vpr is a dynamic protein that primarily localizes in the nucleus, but a significant fraction is concentrated at the nuclear envelope (NE), supporting an interaction between Vpr and components of the nuclear pore complex, including the nucleoporin hCG1. In the present study, we have explored the contribution of Vpr accumulation at the NE to the Vpr functions, including G2-arrest and pro-apoptotic activities, and virus replication in primary macrophages.

Results
In order to define the functional role of Vpr localization at the NE, we have characterized a set of single-point Vpr mutants, and selected two new mutants with substitutions within the first α-helix of the protein, Vpr-L23F and Vpr-K27M, that failed to associate with hCG1, but were still able to interact with other known relevant host partners of Vpr. In mammalian cells, these mutants failed to localize at the NE resulting in a diffuse nucleocytoplasmic distribution both in HeLa cells and in primary human monocyte-derived macrophages. Other mutants with substitutions in the first α-helix (Vpr-A30L and Vpr-F34I) were similarly distributed between the nucleus and cytoplasm, demonstrating that this helix contains the determinants required for localization of Vpr at the NE. All these mutations also impaired the Vpr-mediated G2-arrest of the cell cycle and the subsequent cell death induction, indicating a functional link between these activities and the Vpr accumulation at the NE. However, this localization is not sufficient, since mutations within the C-terminal basic region of Vpr (Vpr-R80A and Vpr-R90K), disrupted the G2-arrest and apoptotic activities without altering NE localization. Finally, the replication of the Vpr-L23F and Vpr-K27M hCG1-binding deficient mutant viruses was also affected in primary macrophages from some but not all donors.

Conclusion
These results indicate that the targeting of Vpr to the nuclear pore complex may constitute an early step toward Vpr-induced G2-arrest and subsequent apoptosis; they also suggest that Vpr targeting to the nuclear pore complex is not absolutely required, but can improve HIV-1 replication in macrophages.
The Passivity of the Administration
Authors: Ringeling Arthur 
Published: November 2007

The welfare state claims to provide for its inhabitants. Normally the duration of this provision is specified: from the cradle to the grave. This implies a specific role for the state, the role of distributor of public commodities and services. Among the possible ways of bringing about a distribution of commodities and services in a community, there are two extremes. The one extreme is distribution by way of the market mechanism. The other extreme is distribution by bureaucratic procedure. The development of the welfare state brought with it the transfer of the distribution of public goods from the market sector to the bureaucratic sector, as well as to various intermediate forms.
There are many methods conceivable, by which the government can distribute its commodities and services. It is possible to do it by means of a lottery, as is the case with the admittance to particular university courses in Holland. Another method, based on the adage ‘the early bird catches the worm’, is frequently applied in public transport and theatre performances. One may offer the provision to anyone who is at a particular place, as with traffic lights at a busy crossing.
Daptomycin versus Vancomycin for Complicated Skin and Skin Structure Infections: Clinical and Economic Outcomes
Authors: Davis Susan L. , McKinnon Peggy S. , Hall Levi M. , Delgado George , Rose Warren , Wilson Robert F. , Rybak Michael J. 
Published: November 2007

Study Objective. To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated skin and skin structure infections.Design. Prospective, open‐label study.Setting. Level 1 trauma center in Detroit, Michigan.Patients. Fifty‐three adult patients with complicated skin and skin structure infections at risk for methicillin‐resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin.Intervention. Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5–20 μg/ml.Measurements and Main Results. Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001).Conclusions. Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost‐effective alternative to vancomycin for complicated skin and skin structure infections.
British Diplomacy and the German Problem, 1848-1850
Authors: Orr William J. 
Published: November 2007

Throughout much of the nineteenth century relations between Britain and Germany were blessed not only by the absence of any fundamental conflicts of national interest, but also by positive factors tending to encourage friendly ties. Memories of the common struggle against Napoleon, the predominantly Protestant character of tioth countries, and the marriage of Queen Victoria to a German prince all suggested a natural affinity between them. German liberals and conservatives alike found much to admire in English political institutions, while Englishmen in turn approved the steps, however halting, by which many of the German states adopted constitutions and representative institutions.During the late 1840s British statesmen did appear to have recognized the benefits that would accrue for Britain through consolidation of the German Confederation, and there was also some discussion regarding the prospect of an Anglo-Prussian alliance. After 1846, thanks to Palmerston's stridency in the affair of the Spanish marriages, Britain lost the good will of France and thus remained diplomatically isolated in the face of the powerful conservative coalition of Austria, Prussia, and Russia.
Victorian Pressure Groups: Directions for Research
Authors: Malchow Howard LeRoy 
Published: November 2007

In recent years there has been considerable interest in Victorian politics and the Victorian political system. This has provided a substantial and continuing literature, much of which, however, remains preoccupied with leadership and organization at a parliamentary level. It may, therefore, be valuable to suggest an area within this most traditional of fields which might provide an alternative approach to that of “high politics”—of cabinet intrigue and parliamentary speech-making. In fact, one might ignore, for the moment, Parliament altogether, and consider that side of Victorian political activity which has been largely obscured by Hatfield dinner parties and Highbury foxing. That is, the manner in which Englishmen from outside Westminster, and perhaps from outside the formal institutions of party and government, attempted to determine the substance of issues and solutions debated in Parliament and at Whitehall.One should avoid confusing the visible and symbolic place Parliament has occupied with the reality of political initiative. In England the rapid growth of new economies and the cities they created in the North and Midlands at the beginning of the Victorian age detracted from the centralness of London and Westminster, blurring somewhat the focus of English economic and political life, and creating new urban hierarchies consciously opposed to domination from Whitehall. Within the vast new urban centers, fed by a rural migration and accellerated by the spreading railway system, voluntary associations of all sorts became a peculiarly Victorian characteristic—serving perhaps as surrogates for a sense of community lost in the passage from a rural to an urban environment. Reading and corresponding societies, social clubs, self-help and benevolent associations, charities—this kind of activity penetrated Victorian society from the respectable working classes to the very rich. Related to this social phenomenon was a growth in local and national political associations—what one might today call “cause lobbies.” It is this type of pressure group activity, predominantly urban and probably largely middle-class, which needs to be more systematically studied. This essay will attempt to indicate the value of such research into “low politics,” and to suggest some avenues of approach.
The English Fishing Industry in the Sixteenth Century: The Case of Great Yarmouth
Authors: Tittler Robert 
Published: November 2007

For all the pride which it engendered among contemporaries, who saw in the Tudor fisheries a nursery for English seamen and even a hallmark for the national identity, the fishing industry in the sixteenth century has received scant attention from English historians. This neglect has been doubly unfortunate. On the one hand, it leaves us in general ignorance of the industry itself: its organization, personnel, productivity, and economic importance in both national and regional terms. On the other, it has denied us the opportunity to observe a tradition-bound industry of considerable antiquity as it faced the political, economic, and technological changes of the post-medieval era.The format of an essay cannot reasonably encompass a detailed study of a major industry, but the selection of a particular case for study can at least present a helpful paradigm for the whole, and fill part of the void in the existing literature. The fishing industry of Great Yarmouth seems an appropriate choice. The fact that herring collected off the mouth of the River Yare each September for as far back as man can remember has made the association of Yarmouth and fishing as old as it is logical. Fishermen plied those grounds from at least the sixth century, making the town one of the earliest recorded fishing centres of Northern Europe, and well before the Conquest townsmen had dedicated their parish church to St. Nicholas, patron of fishermen. Throughout the Middle Ages Yarmouth stood alone as the chief supplier of herring, a dietary staple to the English market, and ranked near the top of the European fishing industry.
England Is The Country: Modernization and the National Self-image
Authors: Wiener Martin J. 
Published: November 2007

In the last hundred years the British initiators of the Industrial Revolution have fallen behind one after another of their imitators. As a consequence, the issue of “modernization” has moved to the head of the political agenda in a nation that was for the nineteenth century world the very model of “modernity.” Much of this change in world position was inevitable — yet not all of it. Why, historians have recently been asking, did Britain between 1870 and 1900 lose the economic dynamism that had been her hallmark? Why, further, did the British fail to recover this lost dynamism in the twentieth century?The British experience ought to be of particular interest to Americans today, for recently we have become aware of thecostsas well as the benefits of economic growth. Our faith in material progress is dimming. At the same time, our former economic dynamism seems now in question. Indeed, we may be repeating the experience of Britain.To understand the change in British economic behavior, we must look at more than solely economic history. As Max Weber argued as far back as 1904, economic activity takes place in a wider social context. Attitudes and values play a vital role in shaping economic behavior. Development economists have discovered in the last two decades that economic change is not produced solely by economic means — by introducing technology and capital alone. To some degree at least, societies “choose” their economic futures by the values they hold. Because of this, intellectual and social history may tell us much about the difficulties of continuing modernization in twentieth century Britain.
Pythagorean Proportion and Music of the Spheres inRichard II
Authors: Scott Leighton R. 
Published: November 2007

“The Pythagoreans … defined justice unqualifiedly as reciprocity.”(Aristotle,Eth. Nic.V. 8. 1132b 21)It is one of time's ironies thatRichard II, once troublesome to scholars for its “imperfection,” is now enjoying increasing appreciation for unity and harmony. One modern analysis of imagery even recognizes the play as “a succession of balances” whose theme advances “almost as the proof of a mathematical proposition”(italics mine). Other recent scholarship speaks in terms of a “symphony” of repeated key words and balanced scenes, and still another study defends its “emotional consistency,” and “logical continuity.”Clearly, in spite of some diminution of quality in later acts, what emerges in the end-product is a well-balanced, well-tuned, completely metrical mechanism, whose major moving parts signify interaction, change, and integration in the realms of personal, political, and cosmic order, with an appropriate counterpoint of Pythagorean imagery, e.g., “heaven,” “soul,” “balance,” “time,” and “music” or “harmony.”
A Mid-Victorian Coverup: The Case of The “Combustible Commodore” and the Second Anglo-Burmese War, 1851–1852
Authors: Pollak Oliver B. 
Published: November 2007

The origins of the Second Anglo-Burmese War in late 1851 were the subject of a Mid-Victorian bipartisan and bureaucratic coverup throughout 1852-53. The Government of India in Calcutta had successfully maintained a policy of “non-intercourse” following removal in 1840 of its diplomatic representatives from Burma despite frequent uncoordinated calls for remonstrance by merchants, missionaries and military administrators. In 1851, a convergence of factors, most notably the alleged mistreatment of British subjects in Rangoon, captured the President in Council's attention in Calcutta resulting in a policy change which led to armed intervention. Calcutta's renewed interest in Burma occurred while politicans in London prepared to scrutinize the bureaucratic relations between the London-based Cabinet and the East India Company.Official discussions in Calcutta about Burma occurred while Governor General Dalhousie was “up country on progress” and at the very time that the Council wanted to test its capacity to act independently. The Council resorted to a unit of the Royal Navy then in Calcutta enroute from Acheh to the Persian Gulf. Commodore George Robert Lambert offered to deliver letters to Burmese authorities in Rangoon and negotiate on behalf of the English subjects. Lambert's reputation for moderation recommended him to Calcutta officials. His instructions from Council and private letters from Dalhousie advised caution and the avoidance of confrontation. Yet Lambert, a line officer, ultimately responsible to the Admiralty in London, could conceivably ignore Calcutta's wishes and chart his own course.