Methodological assessment of HCC literature.

Despite the fact that the hepatocellular carcinoma (HCC) represents a major health problem, very few interventions are available for this disease, and only sorafenib is approved for the treatment of advanced disease. Of note, only very few interventions have been thoroughly evaluated over time for HCC patients compared with several hundreds in other, equally highly lethal, tumours. Additionally, clinical trials in HCC have often been questioned for poor design and methodological issues. As a consequence, a gap between what is measured in clinical trials and what clinicians have to face in daily practice often occurs. As a result of this scenario, even the most recent guidelines for treatment of HCC patients use low strength evidence to make recommendations. In this review, we will discuss some of the potential methodological issues hindering a rational development of new treatments for HCC patients.

Pre-analytical and methodological challenges in red blood cell microparticle proteomics.

Microparticles are phospholipid vesicles shed mostly in biological fluids, such as blood or urine, by various types of cells, such as red blood cells (RBCs), platelets, lymphocytes, endothelial cells. These microparticles contain a subset of the proteome of their parent cell, and their ready availability in biological fluid has raised strong interest in their study, as they might be markers of cell damage. However, their small size as well as their particular physico-chemical properties makes them hard to detect, size, count and study by proteome analysis. In this review, we report the pre-analytical and methodological caveats that we have faced in our own research about red blood cell microparticles in the context of transfusion science, as well as examples from the literature on the proteomics of various kinds of microparticles.

The Georgian adolescent health survey: methodological and strategic issues.

OBJECTIVES: To conduct a national survey on adolescent health and lifestyles in Georgia and to thus set up a database on adolescent. METHODS: A two-stage cluster sample of around 8000-10000 in-school 15-18 years adolescents are being reached through a random selection of classes in Georgia. The sample has been stratified by age, region, type of school and language. A self-administered questionnaire of 87 questions has been developed and translated into the four main languages used in Georgia. RESULTS: Up to June 2004, the researchers have reached 511 classes (9306 pupils). In total, 8039 questionnaires have been considered valid. The main concerns encountered for this survey are linked with acceptance of the survey, cross-cultural issues, political and strategic problems as well as inadequate physical environmental support. CONCLUSION: Despite Georgia's unfavourable economical and political situation, it has been possible to run a national survey on the health of adolescents, according to the usual standards used in the field. This survey should allow for 1) the identification of priorities in the field of health care and health promotion 2) the monitoring of adolescent health in the future.

On the use of IRMS in forensic science: proposals for a methodological approach

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensic science denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstrated its potential to distinguish chemically identical compounds coming from different sources. Despite the numerous applications of IRMS to a wide range of forensic materials, its implementation in a forensic framework is less straightforward than it appears. In addition, each laboratory has developed its own strategy of analysis on calibration, sequence design, standards utilisation and data treatment without a clear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose a methodological framework of the whole process using IRMS methods. We emphasize the importance of considering isotopic results as part of a whole approach, when applying this technology to a particular forensic issue. The process is divided into six different steps, which should be considered for a thoughtful and relevant application. The dissection of this process into fundamental steps, further detailed, enables a better understanding of the essential, though not exhaustive, factors that have to be considered in order to obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratory comparisons.

Stroke mortality in the Seychelles: methodological issues.

Comment on: Johnston SC, Mendis S, Mathers CD. Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 2009 Apr;8(4):345-54. PMID: 19233730

On the use of IRMS in forensic science: proposals for a methodological approach

The flourishing number of publications on the use of isotope ratio mass spectrometry (IRMS) in forensicscience denotes the enthusiasm and the attraction generated by this technology. IRMS has demonstratedits potential to distinguish chemically identical compounds coming from different sources. Despite thenumerous applications of IRMS to a wide range of forensic materials, its implementation in a forensicframework is less straightforward than it appears. In addition, each laboratory has developed its ownstrategy of analysis on calibration, sequence design, standards utilisation and data treatment without aclear consensus.Through the experience acquired from research undertaken in different forensic fields, we propose amethodological framework of the whole process using IRMS methods. We emphasize the importance ofconsidering isotopic results as part of a whole approach, when applying this technology to a particularforensic issue. The process is divided into six different steps, which should be considered for a thoughtfuland relevant application. The dissection of this process into fundamental steps, further detailed, enablesa better understanding of the essential, though not exhaustive, factors that have to be considered in orderto obtain results of quality and sufficiently robust to proceed to retrospective analyses or interlaboratorycomparisons.

Food traditions and landscape histories of the Indian Ocean World : theoretical and methodological reflections

Environmental histories of plant exchanges have largely centred on their eco- nomic importance in international trade and on their ecological and social impacts in the places where they were introduced. Yet few studies have at- tempted to examine how plants brought from elsewhere become incorporated over time into the regional cultures of material life and agricultural landscapes. This essay considers the theoretical and methodological problems in inves- tigating the environmental history, diversity and distribution of food plants transferred across the Indian Ocean over several millennia. It brings together concepts of creolisation, syncretism, and hybridity to outline a framework for understanding how biotic exchanges and diffusions have been translated into regional landscape histories through food traditions, ritual practices and articu- lation of cultural identity. We use the banana plant - which underwent early domestication across New Guinea, South-east Asia and peninsular India and reached East Africa roughly two thousand years ago - as an example for il- lustrating the diverse patterns of incorporation into the cultural symbolism, material life and regional landscapes of the Indian Ocean World. We show that this cultural evolutionary approach allows new historical insights to emerge and enriches ongoing debates regarding the antiquity of the plant's diffusion from South-east Asia to Africa.

Vulnerability as a heuristic for interdisciplinary research: Assessing the thematic and methodological structure of empirical life-course studies

Changes in human lives are studied in psychology, sociology, and adjacent fields as outcomes of developmental processes, institutional regulations and policies, culturally and normatively structured life courses, or empirical accounts. However, such studies have used a wide range of complementary, but often divergent, concepts. This review has two aims. First, we report on the structure that has emerged from scientific life course research by focusing on abstracts from longitudinal and life course studies beginning with the year 2000. Second, we provide a sense of the disciplinary diversity of the field and assess the value of the concept of 'vulnerability' as a heuristic tool for studying human lives. Applying correspondence analysis to 10,632 scientific abstracts, we find a disciplinary divide between psychology and sociology, and observe indications of both similarities of-and differences between-studies, driven at least partly by the data and methods employed. We also find that vulnerability takes a central position in this scientific field, which leads us to suggest several reasons to see value in pursuing theory development for longitudinal and life course studies in this direction.

A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.

OBJECTIVE: To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02. METHODS AND MATERIALS: An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART). RESULTS: With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification. CONCLUSIONS: ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.