Biomedical research practice and therapeutic practice: to whom does the human body belong?

Who owns the human body? This issue has been formerly raised about the status of the slave. Today, it has become a prominent stake for when reflecting on biomedical research and healthcare practices. In our cultures, many answers may be given to this question : they are derived from philosophical or theological traditions ; they are borrowed from anthropological, sociological or psychological knowledge ; they may be formulated in a moral or political perspective. All of them give different insights and reveal one of the various dimensions of the question. When examining the status of the body and its relation to the human subject in the various stages of his/her life (including his/her death), one of the main difficulties is to deal with each of these answers and to understand how they meet and interact in the public debate. Another matter is related to the fact that law also plays a crucial role in the process of giving an answer to this question. In our book, A qui appartient le corps humain ? Médecine, politique et droit (Paris, Belles Lettres, 2004), Claire Crignon-De Oliveira and I have tried to deal with both difficulties. In this article, I focus on the meaning of the various law traditions. In western world, the laws are all derived, up to a certain extent, from the Roman tradition. Whether they have chosen to consider the human body as a property or to associate the body to the person, they have taken very different options. However, an examination of the ways laws are elaborated on this topic shows that these two conceptions can meet in unexpected manners and that lawmaking can give creative answers to both the problem of protecting the person and to the requirements of biomedical research and healthcare practices.     

Primary prevention with the ICD in clinical practice: not as straightforward as the guidelines suggest?

At first sight, guidelines for implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death in patients with left ventricular systolic dysfunction seem unambiguous. There are clear cut-off values for ejection fraction, and functional class. However, determination of the ejection fraction itself is not unambiguous, and other risk factors for sudden death that may have a profound effect on risk are not used for decision-making. Furthermore, to obtain a clinically significant impact on survival, expected longevity is important as it can greatly compromise the benefit in elderly patients but underestimate the long-term potential of ICD therapy in younger patients. (Neth Heart J 2009; 17:107–10.)     

Are the recommendations being met in the general practice year of vocational training? Trainees' views in the West Midlands region.

Vocational trainees in the West Midlands who were in their general practice year were sent a postal questionnaire to find out whether there were important differences between the criteria for training of the 1986 West Midland postgraduate education committee (based on national recommendations) and the perceptions of the trainees of their current trainers and practices. The response rate was 86.2% (75 out of 87). Sixty four per cent (48) of trainees reported that they received on average less than the recommended minimum of three hours of teaching time a week. They felt that experience was inadequate in paediatric surveillance (62.7%) and preventive medical care (37.3%). Most trainers gave topic teaching (90.7%), and few used role play (5%). Most of the trainees (52%) had not signed a contract, a third did not get help with recommended allowances, and 37% thought that their progress had not been reviewed. Several trainees commented on the excellence of their training practices, and most of the practices appeared to be keeping to the spirit of the recommendations. There are, however, discrepancies between what some trainees feel they receive and what is recommended.     

How life cycle–based science and practice support the transition towards a sustainable economy

The International Journal of Life Cycle Assessment -     

Genetic and epigenetic alterations in breast cancer: what are the perspectives for clinical practice?

The worldwide incidence of breast cancer affects 1.2 million women each year. In contrast to the high occurrence of this malady, a decline in mortality is reported among industrialized countries. In this respect, both awareness campaigns and substantial progress achieved in therapy and diagnosis allowed for the enhancement of the survival rate in patients with breast cancer. Undoubtedly, oncology research programs played a relevant role in the improvement of therapeutics and diagnostics for breast cancer. Major strides were reported, especially over the last decade and a half, in better understanding molecular and cellular biology events involved in breast cancer pathogenesis and progression of the disease. However, therapeutic approaches for the treatment of patients with breast cancer need further improvement. Therapeutic interventions can chronically compromise both the state of health and quality of life of breast cancer survivors. In addition, current therapeutic approaches have not significantly improved the survival rate in patients with metastatic disease. On these grounds, it is necessary to develop more efficient therapeutics and diagnostic tools, which can improve the health and quality of life of breast cancer survivors and increase the survival rate in patients with metastatic disease. In this respect, the field of cancer research has placed a particular emphasis on the elucidation of genetic and epigenetic alterations that may lead to the pathogenesis of breast cancer and contribute to its progression.     

Lymph node status as a guide to selection of available prognostic markers in breast cancer: the clinical practice of the future?

Prognosticators evaluating survival in breast cancer vary in significance in respect to lymph node status. Studies have shown e.g. that HER2/neu immunohistochemistry or HER2/neu gene amplification analysis do perform well as prognosticators in lymph node positive (LN +) patients but are less valuable in lymph node negative (LN -) patients. We collected data from different studies and tried to evaluate the relative significance of different prognosticators in LN+/LN- patient groups. In LN+ patients HER2/neu and E-cadherin immunohistochemistry were the statistically most significant prognosticators followed by proliferation associated features (mitotic counts by SMI (standardised mitotic index) or MAI (mitotic activity index), or S-phase fraction). Bcl-2 immunohistochemistry was also significant but p53 and cystatin A had no significance as prognosticators. In LN- patients proliferation associated prognosticators (SMI, MAI, Ki-67 index, PCNA immunohistochemistry, S-phase fraction) are especially valuable and also Cathepsin D, cystatin A, and p53 are significant, but HER2/neu or bcl-2, or E-cadherin less significant or without significance. We find that in studies evaluating single prognosticators one should distinguish between prognosticators suitable for LN+ and LN- patients. This will allow the choice of best prognosticators in evaluating the prospects of the patient. The distinction between LN+ and LN- patients in this respect may also be of special value in therapeutic decisions.     

Image guidance in clinical practice – Influence of positioning inaccuracy on the dose distribution for prostate cancer

BackgroundIn order to consider potential positioning errors there are different recipes for safety-margins for CTV-to-PTV expansion. The aim of this study is to simulate the effect of positioning inaccuracy with clinically realistic patient treatment plans.MethodsFor a collective of 40 prostate patients, the isocenter was shifted back appropriately to the applied table shifts after positioning verification, simulating that no positioning correction had been performed and the treatment plans were recalculated. All the treatment fractions with the appropriate isocenter-shifts were added to yield a new plan considering two scenarios:

• 1)Extreme scenario: summation of only shifted plans.
• 2)Realistic scenario: consideration of the original treatment plan for the fractions with verification imaging.

Afterwards all plans were analysed and compared with each other regarding target coverage, sparing of organs at risk (OAR) and normal tissue complication probability (NTCP).ResultsDose distributions and especially DVH show a deterioration of the target-coverage caused by the positioning inaccuracy. Deviations in dose at a single point can reach values of over 10 Gy. In single cases minimum plan agreement only achieved 66% pass within 3% local dose for the realistic case. Organs at risk and NTCP analysis result in a slightly better sparing of the rectum. Measures of quality like homogeneity and conformity differ just minimally regarding the different scenarios.ConclusionPTV-coverage suffers markedly by the positioning uncertainties, the shifted plans are in large parts clinically not acceptable. Surprisingly sparing of the OAR is not negatively affected by potential positioning errors for this prostate collective.     

Neutrality at sea in transition: State practice in the gulf war as emerging international customary law∗

Abstract

This paper provides an appraisal of the continuing efficacy of the law of neutrality as it pertains to the balance of interests of belligerents and neutrals in the maritime environment. The author finds that international customary law of naval warfare pertaining to the rights of neutrals is emerging today as a result of State and extra‐State practice in the Gulf War. This is demonstrated by examination of belligerent and neutral conduct in the “Tanker War”; and various authoritative assessments of that conduct by the international community. The examination proceeds from an analysis of the underlying theory of the customary law‐making process and evolutionary nature of the law of neutrality since before World War II. State conduct in the Gulf War, including the employment of war‐exclusion zones, is critically examined against this backdrop. Discerned from this analysis are firm, “baseline”; standards of the law of neutrality against which State practice, belligerent as well as neutral, and ultimately the emerging customary law, may be assessed.