bluuebunny/crossref_metadata_2025 huggingface dataset:
Coercive confinement in the Republic of Ireland
Authors: O'Sullivan Eoin , O'Donnell Ian
Published: December 2006

In Ireland until recently, a range of institutions other than prisons was utilized to confine those deemed to be deviant. It seems clear that rather than becoming more punitive (if this is estimated by the number of individuals coercively confined) the country has become considerably less so over the past 50 years. In 1951, despite high emigration providing a safety valve, more than 1 percent of the population was behind closed doors in prisons, borstal, reformatory and industrial schools, psychiatric institutions (as involuntary patients) and homes for unmarried mothers. This was eight times higher than in 2002.
Creating the responsible prisoner
Authors: Bosworth Mary
Published: December 2006

This article examines official management practices and rhetoric in the US federal prison system as they are set out in admission handbooks that are distributed to inmates on arrival. Using concrete examples from contemporary and historical admission manuals I examine the changing language and style of prison governance. Concentrating in particular on the contemporary documents, I show how many of the ideas articulated in the literature on risk and governmentality form the backdrop of everyday prison life as penal administrators attempt to encourage prisoners to govern themselves. In this endeavour, the handbooks rely on a language of managerialism that presents inmates as just another ‘client group’ or customer base. This rhetorical shift implicitly denies the particularity of penal institutions, while simultaneously placing all the responsibility on the prisoners for their self-improvement and good order. The handbooks also reveal women's behaviour and sexuality to be more strictly monitored and regulated than that of men, suggesting that, despite the minimal security risk they pose, women are considered in need of greater control.
Risk analysis and the new practitioner
Authors: Fitzgibbon Diana Wendy M.
Published: December 2006

This aim of this research is to contribute to an examination of the effects of the transition toward risk analysis on the work of practitioners within the criminal justice system, in particular the probation service of England and Wales. The intention here is to focus on the impact on practice and interventions in the shift from traditional casework methods to risk assessment and some of the contradictions and problems this raises. On the basis of a small pilot study, two issues are highlighted: first, whether the successful application of risk assessment systems presupposes the very casework skills which these systems were designed to replace; second, whether deskilled practitioners working under increasing resource constraints tend to inflate the levels of risk presented by clients and mis-refer them to inappropriate cognitive therapy programmes, with the ultimate result that clients needlessly end up in custody.
The other side of clinical trial monitoring; assuring data quality and procedural adherence
Authors: Williams George W
Published: December 2006

BackgroundData monitoring can mean different things. It can mean statistical methodologies for clinical trial monitoring, interim data analysis, monitoring for quality control or assurance or safety reporting to regulatory agencies.

PurposeThe various facets of data monitoring will be discussed and reviewed from primarily an industry perspective.

MethodsBy careful attention to the design and conduct of a clinical trial, the expense of monitoring can be markedly reduced. Careful attention should be given to the qualifications of investigators in the selection of clinical sites and central facilities. Site personnel must be adequately trained. The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial. The monitor should visit the investigator at the site of the investigation frequently enough to ensure acceptable quality. The monitor is responsible for inspecting the case report forms at regular intervals. Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly. The auditor will assess whether the site is being monitored in accordance with the monitoring plan. The determination of the extent and nature of monitoring should be based on considerations such as the objective, design and complexity of the trial. Statistical sampling may be an acceptable method for selecting the data to be verified. The monitor should ensure that adverse events are reported. Study data will be monitored on an ongoing basis to ensure patient safety. The sponsor may utilize a Data Monitoring Committee to protect the validity of a trial.

ConclusionsDiscussions between industry, academia and regulatory groups regarding the optimal extent and methods for monitoring of clinical trials are encouraged.
Cost-effectiveness as an outcome in randomized clinical trials
Authors: Hlatky Mark A , Owens Douglas K , Sanders Gillian D
Published: December 2006

BackgroundEconomic outcomes are now included in many contemporary randomized trials and provide an additional dimension to the assessment of interventions. Economic data collection and analysis pose several methodologic challenges, however.

PurposeThis paper reviews methods of incorporating economic outcomes in clinical trials.

ResultsData on medical resource utilization and cost can readily be collected along with data on clinical outcomes. The cost of planned interventions can be measured with reasonable accuracy, but costs due to unplanned clinical events are more difficult to measure reliably. The total cost depends critically on these relatively infrequent, yet costly, adverse outcomes, which may partially, or even completely, offset any difference between the planned costs of the randomized therapies.

Newer therapies are typically more expensive than older therapies, so the most important question is whether patient outcomes are improved sufficiently to justify the added expense. Cost-effectiveness analysis helps gauge the value provided by a new therapy. The cost-effectiveness of an intervention compared with an alternative is defined as the ratio of the incremental costs and the incremental clinical benefits, measured as dollars per quality-adjusted life-year added. The follow-up period in most clinical trials is generally long enough to measure the added cost of therapy, but may not capture the full benefits of treatment. The limited time horizon of clinical trials makes it necessary to use a model to extrapolate the observed effect of treatment and project the increase in life expectancy. The resulting cost-effectiveness ratio is sensitive to assumptions about the long-term efficacy of treatment, particularly whether the treatment effect will continue or dissipate over time.

ConclusionEconomic outcomes can be measured alongside clinical outcomes in randomized trial. While the use of cost-effectiveness models falls outside the strictly empirical, within-trial analysis framework that is embraced by most clinical trialists, it provides an explicit approach to assessing whether the intervention under study provides a clinically meaningful improvement in outcome that is worthwhile.
Cost-effectiveness analyses alongside randomised clinical trials
Authors: Gray Alastair M
Published: December 2006

BackgroundMany health economists increasingly advocate the use of model-based evaluations rather than trial-based evaluations.

PurposeThe purpose of this paper is to review the merits and limitations of RCT-based evaluations of cost-effectiveness.

ResultsThe paper draws on the examples of large studies such as the United Kingdom Prospective Diabetes Study and the Heart Protection Study to suggest that large randomised trials offer a number of advantages to health economists wishing to estimate cost-effectiveness, including access to patient-level data, unbiased estimates of resource use as well as effects, the estimation of cost-effectiveness in sub-groups of patients, and an enhanced ability to build and validate extrapolation models.

ConclusionsWhile many methodological issues remain to be resolved, the use of patient-level data derived from clinical trials as a basis for economic evaluations is likely to remain an important part of the health economics evidence base, and will also continue to provide the data required for methodological research.
Futility approaches to interim monitoring by data monitoring committees
Authors: DeMets David L
Published: December 2006

Clinical trials involving participants with high risk of serious events or being exposed to a new intervention with potential serious risk are typically monitored during the course of the trial. Often, this monitoring activity is conducted by an independent group of experts, often referred to as a Data Monitoring Committee (DMC). The DMC responsibility includes monitoring for early evidence of a harmful effect or convincing evidence of a benefit. If the data are consistent and overwhelming, the DMC may recommend that a trial be terminated early. Trials may also be terminated early if the initial goal of demonstrating a benefit cannot in all likelihood be attained, or is futile. These are complicated issues and should be sorted out in the protocol and the DMC charter prior to the start of the trial before data begin to accumulate. Several statistical methods have been developed to assist a DMC in determining when a negative or harmful trend is substantial enough to render the trial continuation futile. These will be briefly summarized. However useful these methods might be, they alone are not adequate to make the decision and the DMC must take into account other issues to make a judgment.
Clinical trials bureaucracy: unintended consequences of well-intentioned policy
Authors: Califf Robert M
Published: December 2006

BackgroundAs randomized controlled trials have become the ‘gold standard’ for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects.

PurposeOur purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems.

MethodsWe discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies.

ResultsDespite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians.

ConclusionThe current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.
Generalizing results of randomized trials to clinical practice: reliability and cautions
Authors: Flather Marcus , Delahunty Nicola , Collinson Julian
Published: December 2006

BackgroundWell designed randomized controlled trials provide reliable evidence of treatment effects, but there is no consensus on how best to apply these results to clinical practice. The main concerns are that populations enrolled in trials are more selected than those treated in a clinical setting, and whether the treatment effects observed in trials will also be observed in clinical practice.

MethodsAn informal literature review was undertaken to find studies analysing the issue of generalizing trial results (external validity) to clinical practice.

ResultsMost of the studies focused on differences in patients characteristics (age, gender, severity of disease, concomitant treatments and so on) between the clinical trial population and a ‘real world’ clinical population. None provided good evidence of a reduction in the treatment effect in the trial compared to what might happen in clinical practice for simple pharmacological treatments. However complex treatments like surgery or percutaneous interventional procedures, had a greater potential for variation. Extrapolating treatments to different health care settings from the trial can result in important variations in treatment effects.

ConclusionsComplex therapies need careful consideration before they can be applied routinely from trials into practice, and applying results from one health care environment to a different one should be carried out with caution. Generalizing results from well conducted trials to clinical practice can mostly be carried out with confidence, especially for simple therapies with good evidence of benefit.
Current controversies in data monitoring for clinical trials
Authors: Pocock Stuart J
Published: December 2006

This article presents some real-life challenges faced by clinical trial Data Monitoring Committees (DMCs), with the aim of clarifying some of the controversial issues that relate to both statistical stopping boundaries and DMC decision-making. Specific attention is given to what constitutes a sensible statistical boundary for stopping a trial early for benefit, bearing in mind that one usually needs proof beyond reasonable doubt of a treatment benefit sufficient to alter future clinical practice. Appropriate choices of stopping boundary for harm and futility are also discussed. The examples serve to illustrate that the practicalities of DMC decision-making require wise judgements based on a totality of evidence, making any statistical boundary just an objective guideline rather than a definitive stopping rule.
The Professional and Organizational Socialization of New English Headteachers in School Reform Contexts
Authors: Crow Gary M.
Published: December 2006

The headteacher's role in school improvement and the changing nature of the role suggest the need to investigate how new school leaders learn their jobs, that is, their socialization to the leader role. This study has two purposes: (1) to identify the content and methods used in the professional and organizational socialization experiences of new English headteachers; and (2) to examine how headteachers perceive that these socialization processes affect their roles as headteachers. The study is based on a longitudinal, multi-case study of primary headteachers during their second and third years. The study found that the new headteachers experience what they referred to as traumatic first-year experiences, which involved management issues. They also had to learn how to form important relationships and how to develop self-learning. This learning occurred through professional, organizational and personal socialization methods and reinforced the important role of mentors, teachers, deputies and former headteachers. The study reinforces the need to further examine how new school leaders learn their jobs in complex, reform environments.
Do School Leaders Have a Shelf Life?
Authors: Earley Peter , Weindling Dick
Published: December 2006

This article explores several issues about school leaders, career stages and performance. It draws upon various pieces of research, including the longitudinal study of secondary headteachers which began in the early 1980s at the National Foundation for Educational Research (NFER), to raise some key issues about headteachers' careers, the various stages of headship, and the relationship between length of tenure and school leader performance. The article concludes with some thoughts regarding the future of headship and what needs to be done to ensure that the quality of leadership remains as good as it should be. If leadership at the apex of organisations is as crucial as all the research and inspection evidence suggests, then what needs to be done to ensure a longer ‘shelf life’ for school leaders and is the notion of a limited or fixed-term contract worth revisiting?
Teacher Leadership in (In)action
Authors: Muijs Daniel , Harris Alma
Published: December 2006

Teacher leadership is a concept that is gaining increasing interest from both practitioners and researchers. This article presents findings from three case studies in the UK that can be characterized as exhibiting developed, emergent and restricted teacher leadership. Differences and similarities between the schools were examined, leading us to conclude that purposive action by the head, school culture and school structures were the key distinguishing factors. Teacher leadership requires active steps to be taken to constitute leadership teams and provide teachers with leadership roles. A culture of trust and collaboration is essential, as is a shared vision of where the school needs to go, clear line management structures and strong leadership development programmes. In the developed and emergent teacher leadership schools, barriers to teacher leadership were mainly external to the school. In the school we described as exhibiting restricted teacher leadership, internal factors were also key barriers.
The ‘Bigger Feeling’
Authors: Woods Glenys
Published: December 2006

This article reports findings from a study of headteachers and spirituality. It is intended to give some insight into the importance of spiritual experience as a phenomenon which enables leaders to be better resourced internally and find deeper meaning, and to provide evidence of the significance and influence of spiritual experience for educational leadership in schools. The study draws on survey and interview data from secondary and primary headteachers in three local education authorities in England.
Lies, distortion and what doesn’t work: Monitoring prison stories in the British media
Authors: Mason Paul
Published: December 2006

This article argues that the populist and highly punitive penal policy in the UK is promoted by media discourses around prison. The combination of over-reporting of violent and sexual crime in the media and fictional constructions of imprisonment has been a highly significant factor in the growth of the prison population in late modernity. Providing a discourse analysis of one month’s UK media output on prison, it argues that through a discourse of dangerousness delivered to a fearful public, prison is constructed unproblematically as a solution to crime, echoing the ‘what works’ mantra of New Labour. The meaning of prison, it argues, is shifted from a place of pain delivery to one which treats and trains. The article further contends that media discourse of the prisoner precludes any rational debate about alternatives to prison. Media representations of incarceration as an institution full of murderers, rapists and paedophiles precludes a long overdue debate about prison suicides, the erosion of prisoners’ rights and the rising number of women and children incarcerated.
‘We might be locked up, but we’re not thick’: Rex Bloomstein’s Kids Behind Bars
Authors: Bennett Jamie
Published: December 2006

Kids Behind Bars (2005) is the latest documentary by Rex Bloomstein, who has been making prison films for over 30 years. This article argues that media representation of prisons plays a role in shaping public perceptions as most people have no direct access to prisons. It is argued that the function of prisons is contested in these representations; while some provide support for punitiveness, others present a case for reform. Using the analysis of Ericson et al. (1991), it is argued that these representations are concerned with aspects of social order: social hierarchy, morality, and procedural form. The article argues that Bloomstein’s films have provided a voice to marginalized people and opened an alternative dialogue about the purpose of imprisonment, thus presenting challenges to established social hierarchy and morality. However, his films have generally presented hope in rehabilitation, thus reinforcing the procedural form. In Kids Behind Bars, the way Bloomstein has structured the film represents that the imprisonment of children has a detrimental impact, thus challenging the institution of child imprisonment. As such, this is Bloomstein’s most radical prison film. The article concludes with an interview with Rex Bloomstein, where he discusses this film.
Smart on crime: The new language for prisoner release
Authors: Altheide David L. , Coyle Michael J.
Published: December 2006

This exploratory study of news media reports examines language of incarceration shifts from ‘tough on crime’ to ‘smart on crime’ as a feature of broader, contextual meanings about: (1) the costs and benefits of prison and incarceration; (2) the moral meanings and ‘practical reasoning’ associated with imprisonment; (3) the language of deviance and respectability. This work is linked to two long-term projects. One is the ‘discourse of fear’, the pervasive communication, symbolic awareness, and expectation that danger and risk are a central feature of everyday life. The other is ‘the language of justice’, or a discourse analysis of justice speech and the construction of social control. Our aim in this project is to explore the changing discourse of incarceration. News reports were selected and analyzed using ethnographic content analysis and ‘tracking discourse’, or following certain issues, words, themes, and frames over a period of time, across different issues, and across different news media. We find that ‘smart on crime’ did promote more lenient sentences for less demonized offenders, but the message was more receptive to news organizations if delivered by claims makers associated with criminal justice organizations. Some implications for claims making and the social construction of reality are discussed.
Cultural criminology and kryptonite: Apocalyptic and retributive constructions of crime and justice in comic books
Authors: Phillips Nickie D. , Strobl Staci
Published: December 2006

The current study utilizes a cultural criminological approach to examine paradigms of justice portrayed in American comic books. Based on a review of the literature, we hypothesize that the dominant crimes depicted in comic books are violent street crimes and that the portrayed responses to these crimes are executed outside the rule of law by an avenging protagonist. According to the literature surveyed, comic book protagonists seek to restore public order as a means of returning the community to a constructed, nostalgic ideal. Moreover, the implied policy message in comic books is one of vigilantism, in which moral justice trumps legitimate criminal procedure. Based on a content analysis of 20 contemporary best-selling comic books, themes of organized crime, often involving complex transnational networks, are more prevalent than street crimes, contrary to our hypothesis. However, the response to crime remains focused on vigilante methods and on the restoration of a constructed utopic community that espouses the rule of law.
Fixation du lithium en traces dans une phengite de synthèse
Authors: Maurel P. , Volfinger M.
Published: December 2006

On effectue la synthèse hydrothermale d'une phengite à partir d'un gel de composition 90% muscovite-10% céladonite, en présence de chlorure de lithium, à 500°C, 1000 bars. Le produit final obtenu contient environ 2000 ppm de Li. L'étude de la cinétique de la dissolution, en milieu HCl 2·4 n, des éléments majeurs et du lithium montre que 33% du lithium sont très faiblement liés au mica et vraisemblablement adsorbés. Ce qui reste de Li entre en substitution isomorphique dans le réseau de la phengite, sans doute en sites octaédriques.
Origin of Middle Jurassic and Lower Cretaceous fuller's earths in England
Authors: Jeans C. V. , Merriman R. J. , Mitchell J. G.
Published: December 2006

The controversy on the origin of the English Mesozoic fuller's earths is reviewed. Findings of (1) unaltered, devitrified, zeolitized and argillized glass, (2) fragments of holocrystalline and hypocrystalline igneous rocks, and (3) high temperature feldspar and sphene, conclusively demonstrate their volcanic origin. The bulk chemistries of the Bathonian and Lower Cretaceous earths are similar and suggest derivation from ash of trachytic composition. The two earths can be differentiated mineralogically and petrographically by: (a) the presence of sphene, and zeolites replacing glass in the Lower Cretaceous earths; (b) the presence of minor amounts of basaltic glass in the Bathonian earths.

K/Ar radioisotope dating on high-temperature alkali feldspar gives (1) 152–159 Ma for the Bathonian fuller's earth, and (2) 118–125 Ma and 142–148 Ma for the Lower Cretaceous fuller's earths. The distribution of the Mesozoic fuller's earths and the origin of their parent ash is discussed.
Absorption de composes humiques par une montmorillonite H+, Al3+ Présence de smectites à couches interfoliaires organo-minérales dans les andosols
Authors: Moinereau J.
Published: December 2006

L'auteur étudie l'absorption par une montmorillonite H-AI, d'acides organiques extraits d'Andosols dans une gamme de pH allant de 1,5 à 5. Quand il y a absorption entre les feuillets, on observe une résistance particulière de la montmorillonite à l'écrasement après chauffage, même pour des températures supérieures à 500°C Un complexe organo-minéral ou organique résistant à la chaleur se forme entre les feuillets de la montmorillonite, comme le révèlent les courbes d'ATD et les spectres IR. On retrouve les propriétés originelles de la montmorillonite par peroxydation.

Des argiles gonflantes 2/1 à complexes organo-minéraux et/ou organiques entre les feuillets sont observées dans les Andosols. Les propriétés de telles argiles rappellent en partie celles des chlorites gonflantes ou des pseudochlorites.
Convergence de comportement entre les interstratifies kaolinite-smectite et les fire-clays
Authors: Thiry M. , Weber F.
Published: December 2006

L'étude de fire-clays provenant de deux séries continentales d'âge Eocène inférieur montre des corrélations très nettes entre la fréquence des défauts d'empilement des feuillets et certaines propriétés qui opposent les fire-clays aux kaolinites bien ordonnées: faible taux de ‘gonflement’ à l'hydrazine, capacité d'échange cationique élevée. Ces faits ainsi que les filiations observés dans l'une des séries étudiées entre interstratifiés smectitekaolinite et fire-clay condusient à émettre l'hypothèse que les défauts de structure des fire-clays sont dus à la présence de feuillets de type smectite, interstratifiés à faible fréquence, entre les feuillets de type kaolinite.
Nontronite: chemistry and x-ray diffraction
Authors: Eggleton R. A.
Published: December 2006

Chemical and X-ray analysis of eight samples of nontronite are consistent with the Hofmann et al. montmorillonite structure. The finest fraction of some fully hydrated (15·3 Å) samples is composed of crystals all about 6 or 7 unit cells thick, and having 12 H2O per 8 Si, arranged at three levels in the interlayer, possibly as upright octahedra. During dehydration, non-integral 00l sequences, and variations in d001 result from a range of layer thickness in one crystal, caused by loss of water from the crystal periphery with consequent margin collapse. At about 50% relative humidity, the H2O content of nontronite is determined by the tetrahedral aluminium, probably because Aliv controls maximum crystal size.
Alteration of allophane and imogolite by alkaline digestion
Authors: Farmer V. C. , Smith B. F. L. , Tait J. M.
Published: December 2006

Since digestion of imogolite or allophane in 5% Na2CO3 at 95°C for periods of 2–100 h leads to solid products different in structure and composition from the starting materials, the procedure is unsuitable for selective dissolution of reactive silica-alumina gels from complex clay mixtures. Cold 5% Na2CO3 does not alter these clays, but effects partial solution, the extent of which depends on the degree of dispersion of the clay and the ratio of solids to solution.
Preparation and properties of some hydroxy-aluminium beidellites
Authors: Brindley G. W. , Sempels R. E.
Published: December 2006

Hydroxy-aluminium beidellites are prepared by treating Na-saturated beidellites from Taiwan, with compositions intermediate between end-member beidellite and end-member montmorillonite, with hydroxy-aluminium solutions having OH/Al ratios mainly between 2·00 and 2·50. Chemical analyses show that hydroxy-aluminium ions have compositions near Al6(OH,O)16 and charges near 1·0 in two cases, and near 2·2 in a third case. The basal spacing of the prepared clays is near 17 Å and remains without collapse up to 500°C. Argon adsorption measurements at liquid nitrogen temperatures, after heat-treatment up to 325°C in vacuo overnight, give surface areas near 500 m2/g when the exchangeable Na ions are about one-third replaced by hydroxy-aluminium, but near 200 m2/g when wholly replaced by hydroxy-aluminium. In the latter case the hydroxy-aluminium covers the internal surfaces of the clay almost completely prior to the heat-treatment.
Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial
Authors: Moorman Anthony V. , Harrison Christine J. , Buck Georgina A. N. , Richards Sue M. , Secker-Walker Lorna M. , Martineau Mary , Vance Gail H. , Cherry Athena M. , Higgins Rodney R. , Fielding Adele K. , Foroni Letizia , Paietta Elisabeth , Tallman Martin S. , Litzow Mark R. , Wiernik Peter H. , Rowe Jacob M. , Goldstone Anthony H. , Dewald Gordon W. ,   on behalf of the Medical Research Council (MRC)/National Cancer Research Institute (NCRI) Adult Leukaemia Working Party of the United Kingdom and the Eastern Cooperative Oncology Group
Published: December 2006

Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21;q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.
Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
Authors: Castronuovo Cynthia C , Sacca Paula A , Meiss Roberto , Caballero Fabiana A , Batlle Alcira , Vazquez Elba S
Published: December 2006

Background

Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR) triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB), after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC).

Methods

The intoxication protocol was designed based on previous studies demonstrating that preneoplastic lesions were evident after 89 days of chemical carcinogen administration. Male CF1 mice (n = 18) were used. HR group received DAB (0.5 % w/w) in the diet for 78 days followed by 11 days of carcinogen deprivation. The HC group received the carcinogen and control animals the standard diet during 89 days. The expression of cell cycle related proteins, of Bcl-2 and of HO-1 were analyzed by western blot. The cellular localization and expression of HO-1 were detected by immnunohistochemistry.

Results

Increased expression of cyclin E/CDK2 was observed in HR, thus implicating cyclin E/CDK2 in the liver regenerative process. p21cip1/waf1 and Bcl-2 induction in HC was restituted to basal levels in HR. A similar response profile was found for HO-1 expression levels, showing a lower oxidative status in the carcinogen-deprived liver. The immunohistochemical studies revealed the presence of macrophages surrounding foci of necrosis and nodular lesions in HR indicative of an inflammatory response. Furthermore, regenerative cells displayed changes in type, size and intensity of HO-1 immunostaining.

Conclusion

These results demonstrate that the regenerative capacity of the liver is still observed in the pre-neoplastic tissue after carcinogen withdrawal suggesting that reversible mechanism/s to compensate necrosis and to restitute homeostasis are involved.
Is the Pain Stages of Change Questionnaire (PSOCQ) a useful tool for predicting participation in a self-management programme? Further evidence of validity, on a sample of UK pain clinic patients
Authors: Carr Jane L , Moffett Jennifer A Klaber , Sharp Donald M , Haines Derek R
Published: December 2006

Background

In the context of finite health resources, encouraging self-management of chronic conditions is important. Indeed, it is a key priority in the UK. An increasing number of self-management programmes are becoming available. However, patients may not always choose to participate in them. Some will prefer a more directed or medically orientated treatment. The acceptability of self-management programmes for patients suffering from chronic pain is an important issue. Few measures exist that examine the process of change to a self-management approach. The Pain Stages of Change Questionnaire (PSOCQ) was evaluated for this purpose in the present study. Hypotheses were centred around criterion and construct validity of the PSOCQ.

Methods

A sample of pain patients was surveyed about their interest in participating in a lay-led self-management programme ('the Expert Patients Programme'). In addition, participants completed two psychometric measures: the Pain Stages of Change Questionnaire (PSOCQ) together with the Chronic Pain Acceptance Questionnaire (CPAQ). This is the first study as far as we are aware to examine these two scales together. The psychometric properties of the PSOCQ were examined. Analyses focused on the associations between the PSOCQ scores and interest in participating in the self-management programme. Further associations were examined between the PSOCQ and the Chronic Pain Acceptance Questionnaire.

Results

The results demonstrated qualified support for the PSOCQ, in particular the Contemplation sub-scale. There was a significant positive association between interest and likelihood of joining the self-management programme and contemplation scores. The action and maintenance sub-scales appeared to be measuring a unitary dimension. The associations between the PSOCQ and the Chronic Pain Acceptance Questionnaire were in the directions predicted. The limitations of the study were discussed.

Conclusion

The results showed some support for the PSOCQ as a potentially useful tool in assessing who may or may not be likely to join a self-management course.
Structure of the yeast histone H3-ASF1 interaction: implications for chaperone mechanism, species-specific interactions, and epigenetics
Authors: Antczak Andrew J , Tsubota Toshiaki , Kaufman Paul D , Berger James M
Published: December 2006

Background

The histone H3/H4 chaperone Asf1 (anti-silencing function 1) is required for the establishment and maintenance of proper chromatin structure, as well as for genome stability in eukaryotes. Asf1 participates in both DNA replication-coupled (RC) and replication-independent (RI) histone deposition reactions in vitro and interacts with complexes responsible for both pathways in vivo. Asf1 is known to directly bind histone H3, however, high-resolution structural information about the geometry of this interaction was previously unknown.

Results

Here we report the structure of a histone/histone chaperone interaction. We have solved the 2.2 Å crystal structure of the conserved N-terminal immunoglobulin fold domain of yeast Asf1 (residues 2–155) bound to the C-terminal helix of yeast histone H3 (residues 121–134). The structure defines a histone-binding patch on Asf1 consisting of both conserved and yeast-specific residues; mutation of these residues abrogates H3/H4 binding affinity. The geometry of the interaction indicates that Asf1 binds to histones H3/H4 in a manner that likely blocks sterically the H3/H3 interface of the nucleosomal four-helix bundle.

Conclusion

These data clarify how Asf1 regulates histone stoichiometry to modulate epigenetic inheritance. The structure further suggests a physical model in which Asf1 contributes to interpretation of a "histone H3 barcode" for sorting H3 isoforms into different deposition pathways.
A novel genetic system for recombinant protein secretion in the Antarctic Pseudoalteromonas haloplanktis TAC125
Authors: Cusano Angela Maria , Parrilli Ermenegilda , Marino Gennaro , Tutino Maria Luisa
Published: December 2006

Background

The final aim of recombinant protein production is both to have a high specific production rate and a high product quality. It was already shown that using cold-adapted bacteria as host vectors, some "intractable" proteins can be efficiently produced at temperature as low as 4°C.

Results

A novel genetic system for the production and secretion of recombinant proteins in the Antarctic Gram-negative bacterium Pseudoalteromonas haloplanktis TAC125 was set up. This system aims at combining the low temperature recombinant product production with the advantages of extra-cellular protein targeting.

The psychrophilic α-amylase from Pseudoalteromonas haloplanktis TAB23 was used as secretion carrier. Three chimerical proteins were produced by fusing intra-cellular proteins to C-terminus of the psychrophilic α-amylase and their secretion was analysed. Data reported in this paper demonstrate that all tested chimeras were translocated with a secretion yield always higher than 80%.

Conclusion

Data presented here demonstrate that the "cold" gene-expression system is efficient since the secretion yield of tested chimeras is always above 80%. These secretion performances place the α-amylase derived secretion system amongst the best heterologous secretion systems in Gram-negative bacteria reported so far. As for the quality of the secreted passenger proteins, data presented suggest that the system also allows the correct disulphide bond formation of chimera components, secreting a fully active passenger.
The use of genotyping in antimalarial clinical trials: a systematic review of published studies from 1995–2005
Authors: Collins William J , Greenhouse Bryan , Rosenthal Philip J , Dorsey Grant
Published: December 2006

Background

The use of genotyping to distinguish recrudescent from new infections is currently recommended for all clinical antimalarial efficacy trials by the World Health Organization. However, genotyping-adjusted drug efficacy estimates may vary between trials due to the use of different genotyping methods and to the different settings in which these methods are applied.

Methods

A systematic review of all clinical antimalarial efficacy trials published from 1995–2005 was performed to characterize the use of genotyping, including the methods used and the effect of these methods on estimates of drug efficacy.

Results

In a multivariate analysis, the method of interpretation of genotyping results, the studied therapy, the location of the trial, and the duration of study follow-up all had statistically significant effects on the percent of genotyped outcomes classified as new infections.

Conclusion

Criteria for defining appropriate, standardized genotyping methods for use in different settings are needed to enable more accurate estimates of antimalarial drug efficacy and better comparison between trials. The advantages and disadvantages of different genotyping methods and their potential impact in various settings are discussed.
C60-Fullerenes: detection of intracellular photoluminescence and lack of cytotoxic effects
Authors: Levi Nicole , Hantgan Roy R , Lively Mark O , Carroll David L , Prasad Gaddamanugu L
Published: December 2006

We have developed a new method of application of C60 to cultured cells that does not require water-solubilization techniques. Normal and malignant cells take-up C60 and the inherent photoluminescence of C60 is detected within multiple cell lines. Treatment of cells with up to 200 μg/ml (200 ppm) of C60 does not alter morphology, cytoskeletal organization, cell cycle dynamics nor does it inhibit cell proliferation. Our work shows that pristine C60 is non-toxic to the cells, and suggests that fullerene-based nanocarriers may be used for biomedical applications.
Barriers to the dissemination of four harm reduction strategies: a survey of addiction treatment providers in Ontario
Authors: Hobden Karen L , Cunningham John A
Published: December 2006

A sample of service providers at addictions agencies' in Ontario were interviewed by telephone to assess attitudes toward, anticipated internal and external barriers to implementing, and expected benefits of four harm reduction strategies: needle exchange, moderate drinking goals, methadone treatment, and provision of free condoms to clients. Respondents were also asked to define harm reduction, list its most important elements, and describe what they find most troubling and most appealing about harm reduction. Attitudes toward harm reduction in general and the services provided at each agency were also assessed. Results indicated that the service providers surveyed had positive attitudes toward each of the four harm reduction strategies and harm reduction in general, and the majority of respondents were aware of the benefits associated with each strategy. Almost all of the agencies surveyed allowed for moderate drinking outcomes in the treatment of alcohol problems, and most agencies provided free condoms to clients. In terms of barriers, anticipated negative community reaction to needle exchange, methadone treatment, and free condoms was a major concern for the majority of respondents. Lack of staff, of funding, or anticipated staff resistance were also cited as potential barriers to introducing these strategies. In the case of methadone maintenance, the unavailability of a qualified physician was listed as the primary constraint. Implications for future efforts directed at encouraging the adoption of these strategies and suggestions for future research are discussed.
An examination of the psychometric structure of the Multidimensional Pain Inventory in temporomandibular disorder patients: a confirmatory factor analysis
Authors: Andreu Yolanda , Galdon Maria J , Durá Estrella , Ferrando Maite , Pascual Juan , Turk Dennis C , Jiménez Yolanda , Poveda Rafael
Published: December 2006

Background

This paper seeks to analyse the psychometric and structural properties of the Multidimensional Pain Inventory (MPI) in a sample of temporomandibular disorder patients.

Methods

The internal consistency of the scales was obtained. Confirmatory Factor Analysis was carried out to test the MPI structure section by section in a sample of 114 temporomandibular disorder patients.

Results

Nearly all scales obtained good reliability indexes. The original structure could not be totally confirmed. However, with a few adjustments we obtained a satisfactory structural model of the MPI which was slightly different from the original: certain items and the Self control scale were eliminated; in two cases, two original scales were grouped in one factor, Solicitous and Distracting responses on the one hand, and Social activities and Away from home activities, on the other.

Conclusion

The MPI has been demonstrated to be a reliable tool for the assessment of pain in temporomandibular disorder patients. Some divergences to be taken into account have been clarified.
HLA-C locus alleles may modulate the clinical expression of psoriatic arthritis
Authors: Queiro Ruben , Gonzalez Segundo , López-Larrea Carlos , Alperi Mercedes , Sarasqueta Cristina , Riestra Jose Luis , Ballina Javier
Published: December 2006

The aim of the present study was to evaluate the relative contribution of human leukocyte antigen (HLA)-C locus alleles in determining the risk and the clinical expression of psoriatic arthritis (PsA). One hundred PsA patients were randomly selected and grouped into three disease subsets: oligoarthritis (n = 40), polyarthritis (n = 25) and spondylitis (n = 35). The HLA-C locus profile of this cohort was studied by methods based on molecular biology and was compared with that of 45 patients with psoriasis vulgaris and 177 healthy blood donors from the same ethnic origin. HLA-Cw*0602 was found associated with both psoriasis (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.1 to 12.5; p < 0.0001) and PsA (OR 6.2; 95% CI 3.6 to 10.8; p < 0.0001); however, this allele was equally found among the PsA subsets. HLA-Cw6-positive patients showed a longer psoriasis-arthritis latency period (p = 0.012). HLA-Cw*0701 was found under-represented in PsA in comparison with controls (OR 0.5; 95% CI 0.3 to 0.9; p = 0.04), as was HLA-Cw*0802 (OR 0.3; 95% CI 0.08 to 1; p = 0.05). A positive association was found between psoriatic spondylitis and HLA-Cw*0702 (OR 5.0; 95% CI 1.4 to 25; p = 0.01). HLA-Cw*0602 seems to confer a general risk for psoriasis, but the presence of other HLA-C locus alleles may explain an additional arthritogenic risk. HLA-C alleles may modulate some aspects of the clinical expression of PsA, but these findings need confirmation.
Inferring steady state single-cell gene expression distributions from analysis of mesoscopic samples
Authors: Mar Jessica C , Rubio Renee , Quackenbush John
Published: December 2006

Background

A great deal of interest has been generated by systems biology approaches that attempt to develop quantitative, predictive models of cellular processes. However, the starting point for all cellular gene expression, the transcription of RNA, has not been described and measured in a population of living cells.

Results

Here we present a simple model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels.

Conclusion

Although the model describes a microscopic process occurring at the level of an individual cell, the supporting data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems.