Search

In France, since January 2020, laboratories have started to make available genome-wide Non-Invasive Prenatal Testing (GW-NIPT) beyond the three common trisomies (T21, T13 and T18) at the same cost as standard NIPT. With the possible margins for interpretation of the legal framework and in the absence of clear and updated guidelines, health professionals are left with questions about which type of screening offer may be clinically responsible, morally appropriate, and, at the same time, respectful of women’s values and ability to make autonomous choices. The aim of this study is to provide an analysis and understanding of the challenging dimensions of clinical practices in the context of evolving scientific knowledge and techniques in prenatal genomics. In this article, we develop a critical analysis of the arguments and concerns that emerge around the offer of expanded NIPT and are discussed by health professionals and scientists. To achieve this, we conducted qualitative semi-structured interviews with 17 health professionals and scientists from September 2021 to February 2022 and a comprehensive literature review (regulatory, scientific, medical, institutional sources). The results of our empirical research highlight the importance of addressing ethical issues related to the differing quality of counselling, the complexity of achieving informed consent, and the avoidance of harm to pregnant women in the feedback of findings beyond T21, T18 and T13. If there is an increase in the provision of GW-NIPT within the French public health system, it will be essential to promote medical practices that respect reproductive choices of women, support their autonomous decision and their understanding of the limitations and uncertainties associated with GW screening. Further research is required to provide an insight into women’s perceptions in order to refine our analysis from the patients’ perspective.

Dans cet article, nous analysons comment les questions éthiques relatives à l’introduction du dépistage prénatal non invasif (DPNI) dans les systèmes de santé publique d’Angleterre, de France et d’Allemagne sont discutées différemment selon les pays, en écho aux différentes particularités culturelles et socio-politiques. La comparaison internationale entre ces trois pays montre comment chaque pays définit le principe de l’autonomie reproductive différemment et le met en balance avec d’autres principes et valeurs, tels que la dignité humaine et le devoir de diligence des professionnels de la santé. Cet article repose sur une analyse documentaire qui se concentre sur les arguments et les réglementations des tests prénataux et des choix reproductifs (spécifiquement sur le DPNI), à travers l’investigation de sources réglementaires, parlementaires, scientifiques, médicales, associatives, institutionnelles et médiatiques. In this paper, we analyse how the issues ethical related to the introduction of non-invasive prenatal testing (NIPT) into the public health systems of England, France and Germany are discussed differently across countries, echoing the different cultural and socio-political particularities. The international comparison between these three countries shows how each country defines the principle of reproductive autonomy and weighs it against other principles and values, such as, human dignity and the duty of care of health professionals. This article is based on a literature review that focuses on arguments and regulations of prenatal testing and reproductive choices (specifically on NIPT), through the investigation of regulatory, parliamentary, scientific, medical, association, institutional and media sources.

OBJECTIVES: Advances in genetic technologies provide opportunities for patient care and ethical challenges. Clinical care of patients with rare Mendelian disorders is often at the forefront of those developments. Whereas in classical polygenic inflammatory bowel disease the predictive value of genetic variants is very low, predictive prenatal genetic diagnosis can inform families at high risk of severe genetic disorders. Patients with IL10 signalling defects due to pathogenic variants in IL10RA, Il10RB and IL10 develop severe infantile onset inflammatory bowel disease that is completely penetrant and has a high morbidity and substantial mortality despite treatment. METHODS: We performed a survey among tertiary specialist paediatric centers of 10 countries on the utilisation of predictive prenatal genetic diagnosis in IL-10 signalling defects. We retrospectively report prenatal genetics in a series of 8 families. RESULTS: International variation in legislation, guidelines, expert opinion, as well as cultural and religious background of families and clinicians results in variable utilization of preimplantation and prenatal genetic testing for IL-10 signalling defects. Eleven referrals for prenatal diagnosis for IL-10 signalling defects were identified across four countries. We report on 8 families who underwent prenatal preimplantation monogenic testing after in vitro fertilization (n = 2) and/or by amniocentesis/chorion villus sampling (n = 6). A genetic diagnosis was established in one foetus and excluded in 7 foetuses (all IL10RA variants). CONCLUSIONS: Prenatal genetic testing for IL10R-defects is feasible, yet the legal and ethical considerations are complex and controversial. In some countries, predictive genetics for IL-10-related signalling defects is entering clinical practice.

Background A new nationally commissioned NHS England Genomic Medicine Service (GMS) was recently established to deliver genomic testing with equity of access for patients affected by rare diseases and cancer. The overarching aim of this research is to evaluate the implementation of the GMS during its early years, identify barriers and enablers to successful implementation, and provide recommendations for practice. The focus will be on the use of genomic testing for paediatric rare diseases. Methods This will be a four-year mixed-methods research programme using clinic observations, interviews and surveys. Study 1 consists of qualitative interviews with designers/implementers of the GMS in Year 1 of the research programme, along with documentary analysis to understand the intended outcomes for the Service. These will be revisited in Year 4 to compare intended outcomes with what happened in practice, and to identify barriers and facilitators that were encountered along the way. Study 2 consists of clinic observations (pre-test counselling and results disclosure) to examine the interaction between health professionals and parents, along with follow-up interviews with both after each observation. Study 3 consists of a longitudinal survey with parents at two timepoints (time of testing and 12 months post-results) along with follow-up interviews, to examine parent-reported experiences and outcomes. Study 4 consists of qualitative interviews and a cross-sectional survey with medical specialists to identify preparedness, facilitators and challenges to mainstreaming genomic testing. The use of theory-based and prespecified constructs will help generalise the findings and enable integration across the various sub-studies. Dissemination We will disseminate our results to policymakers as findings emerge, so any suggested changes to service provision can be considered in a timely manner. A workshop with key stakeholders will be held in Year 4 to develop and agree a set of recommendations for practice.

Non-invasive prenatal testing (NIPT) has been available commercially in Europe since approximately 2012. Currently, many countries are in the process of integrating NIPT into their publicly funded healthcare systems to screen for chromosomal aneuploidies such as trisomy 21 (Down syndrome), with a variety of implementation models. In 2019, the German Federal Joint Committee (G-BA), which plays a significant role in overseeing healthcare decisions in Germany, recommended that NIPT be reimbursed through public insurance. Following this recommendation, NIPT will be offered on a case-by-case basis, when a pregnant woman, after being counselled, makes an informed decision that the test is necessary in her personal situation. This model differs significantly from many other European countries, where NIPT is being implemented either as a first-tier screening offer available for all pregnancies, or a contingent screen for those with a high probability of foetal aneuploidy (with varying probability cut-offs). In this paper we examine how this unique approach to implementing NIPT in Germany is produced by an ethical and policy landscape resulting from a distinctive cultural and historical context with a significant influence on healthcare decision-making. Due in part to the specific legal and regulatory environment, as well as strong objections from various stakeholders, Germany did not implement NIPT as a first-tier screen. However, as Germany does not currently publicly fund as standard other forms of prenatal aneuploidy screening (such as combined first trimester screening), neither can it be implemented as a screen contingent on specific probability cut-offs. We discuss how German policy reflects the echoes of the past shaping approaches to new biotechnologies, and the implications of this unique model for implementing NIPT in a public healthcare system.

On July 2021, the UK High Court of Justice heard the Case CO/2066/2020 on the application of Heidi Crowter who lives with Down’s syndrome, and Máire Lea-Wilson whose son Aidan has Down’s syndrome. Crowter and Lea-Wilson, with the support of the disability rights campaign, ‘Don’t Screen Us Out’, have been taking legal action against the Secretary of State for Health and Social Care (the UK Government) for a review of the 1967 Abortion Act: the removal of section 1(1)(d) making termination of pregnancy lawful for ‘severe’ fetal indications detected after 24 weeks' gestation. On 23 September 2021, the High Court dismissed the claim. This action came at a time when non-invasive prenatal testing (NIPT) was introduced into the NHS England Fetal Anomaly Screening Programme for the trisomies 21, 13 and 18. The implementation of NIPT has been heavily criticised, in particular by ‘Don’t Screen Us Out’ campaigners, for increasing fetal selection and discrimination of people living with disabilities. The case of Crowter and Lea-Wilson echoes debates in other European countries such as in France and Germany, where the introduction of NIPT in the public healthcare system has provoked equally vehement public reactions and discussions. The comparison between these three countries allows contextualising the public discourses around NIPT and the ground for termination of pregnancy in relation to different socio-cultural and political contexts. We examine how each country, and particularly England, deals with the conflict between the principles of promoting the rights of people living with disabilities and preserving women’s reproductive autonomy.

Since 2019, England, France and Germany have started offering NIPT as a publicly funded second-tier test for common chromosomal aneuploidies (trisomy 21, 18 and/or 13). Despite these benefits, the introduction of NIPT into routine prenatal care also raises a number of ethical concerns. In this paper, we analyse how these issues are discussed differently across countries, echoing the different socio-political particularities and value-systems that shape the use and regulation of NIPT in a specific country. The international comparison between England, France and Germany shows how each country defines the principle of reproductive autonomy and weighs it against other principles and values, such as, human dignity, disability rights and the duty of care of health professionals. In terms of methodology, our literature review focuses on arguments and regulations of prenatal testing and reproductive choices (specifically on NIPT), through the investigation of regulatory, parliamentary, scientific, medical, association, institutional and media sources. The comparative review helps to better understand ethical questions discussed with regard to NIPT, and, more broadly, to prenatal genomic testing, and the limits associated with reproductive autonomy in the three countries studied. Whereas reproductive autonomy is valued in each country, it is understood and implemented differently depending on the socio-cultural context, and on what other principles are evoked and how they are defined.

Mobile applications for digital contact tracing have been developed and introduced around the world in response to the COVID-19 pandemic. Proposed as a tool to support 'traditional' forms of contact-tracing carried out to monitor contagion, these apps have triggered an intense debate with respect to their legal and ethical permissibility, social desirability and general feasibility. Based on a large-scale study including qualitative data from 349 interviews conducted in nine European countries (Austria, Belgium, France, Germany, Ireland, Italy, the Netherlands, German-speaking Switzerland, the United Kingdom), this paper shows that the binary framing often found in surveys and polls, which contrasts privacy concerns with the usefulness of these interventions for public health, does not capture the depth, breadth, and nuances of people's positions towards COVID-19 contact-tracing apps. The paper provides a detailed account of how people arrive at certain normative positions by analysing the argumentative patterns, tropes and (moral) repertoires underpinning people's perspectives on digital contact-tracing. Specifically, we identified a spectrum comprising five normative positions towards the use of COVID-19 contact-tracing apps: opposition, scepticism of feasibility, pondered deliberation, resignation, and support. We describe these stances and analyse the diversity of assumptions and values that underlie the normative orientations of our interviewees. We conclude by arguing that policy attempts to develop and implement these and other digital responses to the pandemic should move beyond the reiteration of binary framings, and instead cater to the variety of values, concerns and expectations that citizens voice in discussions about these types of public health interventions. ispartof: Critical Public Health vol:32 issue:1 pages:5-18 ispartof: location:England status: Published online

Background: A new nationally commissioned NHS England Genomic Medicine Service (GMS) was recently established to deliver genomic testing with equity of access for patients affected by rare diseases and cancer. The overarching aim of this research is to evaluate the implementation of the GMS during its early years, identify barriers and enablers to successful implementation, and provide recommendations for practice. The focus will be on the use of genomic testing for paediatric rare diseases. Methods: This will be a four-year mixed-methods research programme using clinic observations, interviews and surveys. Study 1 consists of qualitative interviews with designers/implementers of the GMS in Year 1 of the research programme, along with documentary analysis to understand the intended outcomes for the Service. These will be revisited in Year 4 to compare intended outcomes with what happened in practice, and to identify barriers and facilitators that were encountered along the way. Study 2 consists of clinic observations (pre-test counselling and results disclosure) to examine the interaction between health professionals and parents, along with follow-up interviews with both after each observation. Study 3 consists of a longitudinal survey with parents at two timepoints (time of testing and 12 months post-results) along with follow-up interviews, to examine parent-reported experiences and outcomes. Study 4 consists of qualitative interviews and a cross-sectional survey with medical specialists to identify preparedness, facilitators and challenges to mainstreaming genomic testing. The use of theory-based and pre-specified constructs will help generalise the findings and enable integration across the various sub-studies. Dissemination: We will disseminate our results to policymakers as findings emerge, so any suggested changes to service provision can be considered in a timely manner. A workshop with key stakeholders will be held in Year 4 to develop and agree a set of recommendations for practice.

L’annonce du plan « France Médecine Génomique 2015 » témoigne de la volonté des pouvoirs publics français de faire de la médecine génomique l’un des éléments phares de la santé publique et de la recherche scientifique nationales. C’est dans ce contexte que la France a annoncé sa coopération avec la Grande-Bretagne, l’un des plus grands leaders mondiaux de la médecine génomique. Une telle collaboration au niveau international impose une réflexion à un cadre normatif commun qui réponde aux nouveaux défis éthiques posés par la médecine génomique. Afin qu’un tel cadre soit adapté aux différents contextes nationaux, il est nécessaire d’identifier et d’analyser les questions éthiques au niveau général et dans leurs contextes particuliers. Dans cette revue, nous discuterons de l’enjeu international de la médecine génomique et, plus précisément, de l’entrée de la France dans la compétition internationale. Nous explorerons ensuite les enjeux éthiques de la médecine génomique en prenant comme étude de cas le contexte prénatal. Nous finirons par une réflexion sur l’impact que peut avoir le contexte national sur la façon dont les questions éthiques émergent en France par rapport à la Grande-Bretagne.

"Introduction: Non-invasive prenatal testing (NIPT) is a rapidly developing genomic technology that is constantly widening its scope and opening up new possibilities in reproductive medicine. Ten years after NIPT has been made commercially available, it is increasingly entering routine antenatal care as either a first- or second-tier test. In England, France and Germany, for example, NIPT has been made available free-of-charge as a second-tier test to women with a higher chance of common chromosomal anomalies. The clinical implementation of NIPT carries benefits but also raises important ethical questions. Our project analyses these questions within their specific contexts in England, France and Germany. Methods: As part of a wider research project, which will involve qualitative methods, we conducted a document analysis to compare arguments about, and regulations governing NIPT in the three countries in: law and policy document; public reports; medical press; academic literature; and media. Results: Despite the similarities between the three countries to offer NIPT as a second-tier screening tool, they exhibit differences with regard to their public discourses about prenatal genomics, screening policies, the risk-thresholds they use, professional regulations and laws. These differences have an impact on the way ethical issues emerge, and questions about the meaning of health, illness and disability, the scope of public health interventions, social inclusion and exclusion as well as reproductive choice are approached in each country. "

Advance directives to refuse treatment (ADs) are legally binding in many Western European countries. Yet, in practice ADs are only rarely used. This chapter explores the influence of different socio-cultural and legal contexts on the implementation of ADs in three European countries: England, Germany and France. More precisely, this chapter focuses on physicians’ perspectives on the law and the reasons given by them for failing to implement it. It will show how physicians’ sense of duty to respect ADs depends on: (1) the definition of the legal status of ADs in a country; (2) the way the law addresses physicians’ concerns regarding the use of ADs (e.g. uncertainty about validity, respect for patient preferences); and (3) the way ADs are discussed in the public (or not). The findings presented are based on literature review and qualitative interviews.

In this chapter, we examine the two dominant healthcare models, public and private, and discuss the extent to which each model can promote empathetic care. We analyse the moral underpinnings of each model - solidarity and individualism - and examine different justifications for the provision of healthcare under each system. We argue that empathy exercised by the individual healthcare professional alone is not enough to ensure empathetic care overall. Rather, the healthcare system as a whole needs to embrace empathy as one of its principles and make it the basis on which it operates. Although the professional code teaches doctors and nurses to engage empathetically with their patients, it is challenging for healthcare professionals to develop, maintain and enact empathy in a system that does not support and foster it. Ensuring empathetic care for all can be better achieved in a system that acknowledges people’s interdependency and mutual responsibilities.

International audience; This paper traces the way autonomy has become a recognised value in health care in France. In a country which based for many years its social fundamentals on the very idea of solidarity, autonomy has long been considered a foreign ‗Anglo-American principle'. Taking the example of the end-of-life debate, the paper shows however how the use of the French term ‗accompagnement' allowed to redefine autonomy and to associate it with the leading moral principle of solidarity. Exploring the arguments used over the past 25 years in professional guidelines, parliamentary reports, ethics committee reports, and legal texts, the authors describe the shift that had happened in public and legal discourses on end-of-life care. The analysis demonstrates how the scope of autonomy had to be limited by other social values such the protection of the dying person, in order to become an accepted social value in its own. The example of the French end-of-life debate shows that depending on how the concept of autonomy is adapted and applied in a specific context, it can be compatible with the idea of solidarity. Such compatibility has been challenged previously in the international bioethics debate. By demonstrating the possibility of combining autonomy and solidarity, this paper makes an important contribution to the international bioethics debate and to the dialogue between countries that are often perceived as significantly different.

Plants adapt to abiotic stress by undergoing diverse biochemical and physiological changes that involve hormone-dependent signaling pathways. The effects of plant hormones can be mimicked by exogenous chemical regulators such as herbicide safeners, which not only enhance stress tolerance but also confer hormetic benefits such as increased vigor and yield. In this study, rice plants growing in normal and saline soils were exposed to abscisic acid (ABA), the safener cyprosulfamide or both compounds together. We found that cyprosulfamide, either alone or in combination with ABA, protected the plants from salinity stress and induced vigorous growth, including the formation of new tillers and early flowering. Proteomic analysis identified several proteins that were induced by stress and/or the chemical treatments, including the late embryogenesis abundant protein OsLEA3, a putative mitochondrial translocase and a putative fumarylacetoacetate hydrolase. The corresponding gene s were induced by stress and/or the individual chemical treatments, but expression dropped back when the stress was removed. However, the combination of ABA and cyprosulfamide prolonged the expression of all three genes beyond the stress period, and allowed the plants to maintain their enhanced growth characteristics. These data support a model involving cooperation between the cyprosulfamide and ABA signaling pathways. Accordingly, it was found that cyprosulfamide induces ABA synthesis more robustly than salinity stress, allowing the two regulators to converge on certain downstream target genes. We discuss the impact of our results on current models for the hormonal regulation of stress response pathways in rice and other plants.

Arabidopsis thaliana plants were treated simultaneously with the fungicide tebuconazole and the phytohormone abscisic acid (ABA). We carried out comparative proteomic and transcriptomic analysis against untreated controls under different stress regimes. The chemicals were applied 24 h before the onset of drought stress (removal of the nutrient medium) or salinity stress (hydroponic culture using 150 mM NaCl), and samples were taken during the stress treatments and after a 24 h recovery period. The combined chemical treatment protected plants against both forms of stress. Difference in-gel electrophoresis revealed 18 and 34 unique protein markers representing induced tolerance to drought and salinity stress, respectively. Most of the markers represented plastid functions (such as CO(2) fixation and photosystem II activity), and their abundance was reduced under stress conditions but maintained at near normal levels in the treated plants. The corresponding transcripts were reduced in abundance primarily under drought stress but not salinity stress, indicating that the signal transduction pathways activated by tebuconazole/ABA treatment depend on the nature of the stress stimulus.

Although bioethics has had an international and universal outlook since its origin, divergent views on ethical questions in health care practice continue to exist across countries, even within the small continent of Europe. In the literature, the liberal approach of Anglo-American bioethics is often seen as opposed to the solidarity-based approach of continental European bioethics. Yet, despite the importance of recognising these different value systems, we believe that the opposition between Anglo-American and European bioethics does not capture the complexity of the situation. Bioethics and health care debates that take place in various countries influence each other and affect the way normative concepts are interpreted and used in different national contexts. If an international approach to bioethics is to be furthered and dialogue between countries improved, the meaning and use of dominant normative concepts in different countries needs to be better explored.

Dignity is one of the most controversial and yet commonly used terms in debates regarding end-of-life issues. The term “dignity” can take various meanings. For example, it can be used to denote the respect owed to an individual person, or to signify the intrinsic value of humankind as a whole. These two different understandings of dignity inevitably lead to different approaches to end-of-life decisionmaking. This article explores the meaning of the term “dignity” in two European countries, England and France. Our analysis compares public debates and legislation on end-of-life-related issues in these two countries. We argue that in England dignity is most commonly understood as respect for individual autonomy, whereas in France dignity usually signifies respect for humanity as a whole. We demonstrate that the difference in the conceptualization of the term leads to different ethical, and hence legal and practical, approaches to end-of-life issues and vulnerable patients. Our particular focus is on (1) withdrawing/withholding life-sustaining treatment, (2) respect for patient preferences, and (3) assistance in dying. Given the difference in the understanding of dignity, and the underlying philosophical approaches, it appears that there is still a long way to go before we can establish common guidelines on end-of-life decisions across Europe and beyond. However, clarifying the use of the term “dignity” in different discussions around Europe could hopefully facilitate this endeavor.

Cet article vise a montrer comment la question morale de l’euthanasie emerge dans une societe et comment elle est abordee dans deux pays, la France et l’Allemagne, qui interdisent de telles pratiques. En effet, chaque societe a son histoire propre avec des specificites en matiere de normes pratiques, sociales et politiques affectant sa gestion de ces questions. C’est donc a travers le debat et les pratiques que nous cherchons a comprendre l’emergence des demandes de mourir, sans pretendre pour autant resoudre ainsi le probleme moral de l’euthanasie. Pour cela, nous avons mene a la fois une recherche documentaire (analyse des dossiers de presse des quotidiens depuis les annees 1970, de la litterature medicale et associative et des textes juridiques) et un travail ethnographique dans trois hopitaux en France et deux en Allemagne (observations participantes au sein des equipes de soins palliatifs entre 2005 et 2007 combinees a 21 entretiens menes aupres de professionnels francais et 20 aupres de professionnels allemands). Malgre les differences constatees dans ces deux pays aux legislations pourtant tres semblables, l’enjeu principal qui emerge de leurs debats respectifs est la question de l’autonomie du malade lorsqu’il veut choisir les conditions dans lesquelles il souhaite mourir.Prat Organ Soins. 2010;41(4):323-330

Photosystem II (PSII) is a huge multi-protein-complex consisting, in higher plants and green algae, of the PS II core and the adjacent light harvesting proteins. In the study reported here, N-terminal His-tags were added to the plastome-encoded α-subunit of cytochrome b559, PsbE, in tobacco plants, thus facilitating rapid, mild purification of higher plant PSII. Biolistic chloroplast transformation was used to replace the wildtype psbE gene by His-tagged counterparts. Transgenic plants did not exhibit an obvious phenotype. However, the oxygen evolution capacity of thylakoids prepared from the mutants compared to the wildtype was reduced by 10–30% depending on the length of the His-tag, although Fv/Fm values differed only slightly. Homoplasmic F1 plants were used to isolate PSII cores complexes. The cores contained no detectable traces of LHC or PsaA/B polypeptides, but the main core subunits of PSII could be identified using immunodetection and mass spectroscopy. In addition, Psb27 and PsbS were detected. The presence of the former was presumably due to the preparation method, since PSII complexes located in the stroma are also isolated. In contrast to previous reports, PsbS was solely found as a monomer on SDS-PAGE in the PSII core complexes of tobacco.

The light-harvesting chlorophyll a/b complex (LHCIIb) spontaneously assembles from its pigment and protein components in detergent solution. The formation of functional LHCIIb can be detected in time-resolved experiments by monitoring the establishment of excitation energy transfer from protein-bound chlorophyll b to chlorophyll a. To detect the possible initial steps of chlorophyll binding that may not yet give rise to chlorophyll b-to-a energy transfer, we have monitored LHCIIb assembly by measuring excitation energy transfer from a fluorescent dye, covalently bound to the protein, to the chlorophylls. In order to exclude interference of the dye with protein folding or pigment binding, the experiments were repeated with the dye bound to four different positions in the protein. Initial chlorophyll binding occurs at roughly the same rate as the establishment of chlorophyll b-to-a energy transfer, in the range of 10 s. However, under limiting chlorophyll concentrations, the binding of chlorophyll a clearly precedes that of chlorophyll b. The complex containing the apoprotein, carotenoids, and chlorophyll a but no chlorophyll b is biochemically unstable and therefore cannot be isolated. However, chlorophyll a binding into this weak complex is specific, as it does not occur with a C-terminal deletion mutant of Lhcb1 which still contains most chlorophyll-ligating amino acids but is unable to fold and assemble into functional LHCIIb. As a scenario for LHCIIb assembly in the thylakoid, we propose the initial formation of a labile Lhcb1-chlorophyll a-carotenoid complex that then becomes stabilized by the binding (or formation in situ) of chlorophyll b.

The major light-harvesting chlorophyll a/b protein (LHCIIb) of higher plants is one of the few membrane proteins that can be refolded in vitro. During folding, the apoprotein is assembled with pigments to form a structurally authentic and functional pigment--protein complex. All reconstitution procedures used so far include solubilization of the apoprotein in sodium dodecyl sulfate (SDS) where the protein adopts approximately half of its alpha-helical folding present in the native structure. This paper shows that this preformed alpha-helix is not a prerequisite for LHCIIb folding in vitro. The apoprotein can also be reconstituted starting from a solution in guanidinium hydrochloride (Gnd) where the protein contains no detectable helical structure. Reconstitution yields are somewhat lower in the Gnd than in the SDS procedure, but the reconstitution products exhibit very similar biochemical and spectroscopic properties. The kinetics of LHCIIb assembly, as assessed by time-resolved fluorescence measurements, are virtually the same in both reconstitution procedures. This demonstrates that the initiation of alpha-helix formation is not a rate-limiting step in LHCIIb apoprotein folding.

This paper presents the results of a qualitative interview study exploring English and French physicians’ moral perspectives and attitudes towards end-of-life decisions when patients lack capacity to make decisions for themselves. The paper aims to examine the importance physicians from different contexts accord to patient preferences and to explore the (potential) role of advance directives (ADs) in each context. The interviews focus on (1) problems that emerge when deciding to withdraw/-hold life-sustaining treatment from both conscious and unconscious patients; (2) decision-making procedures and the participation of proxies/relatives; (3) previous experience with ADs and views on their usefulness; and (4) perspectives on ways in which the decision-making processes in question might be improved. The analysis reveals differences in the way patient preferences are taken into consideration and shows how these differences influence the reasons physicians in each country invoke to justify their reluctance to adhering to ADs. Identifying cultural differences that complicate efforts to develop the practical implementation of ADs can help to inform national policies governing ADs and to better adapt them to practice.

In Western societies advance directives are widely recognised as important means to extend patient self-determination under circumstances of incapacity. Following other countries, England and France have adopted legislation aiming to clarify the legal status of advance directives. In this paper, I will explore similarities and differences in both sets of legislation, the arguments employed in the respective debates and the socio-political structures on which these differences are based. The comparison highlights how different legislations express different concepts emphasising different values accorded to the duty to respect autonomy and to protect life, and how these differences are informed by different socio-political contexts. Furthermore each country associates different ethical concerns with ADs which raise doubts about whether these directives are a theoretical idea which is hardly applicable in practice. © 2012 Springer Science+Business Media, LLC.

The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to four quinolones (moxifloxacin, clinafloxacin, trovafloxacin and ciprofloxacin) were determined, as well as to cefoxitin, clindamycin, metronidazole, imipenem and ticarcillin-clavulanic acid. The results for the latter five agents were compared with those of a study on 200 isolates done 6 years previously. Clinafloxacin and trovafloxacin were the most active agents tested with MIC90s lower than all other antimicrobials except imipenem. Susceptibility rates for imipenem, ticarcillin- clavulanic and metronidazole continue to be high, although resistant strains are emerging. For ticarcillin-clavulanic acid and metronidazole, MIC90s increased four- to eight-fold for the B. fragilis species between the two study periods.

End-of-life care practices and attitudes in Europe are highly diverse, which is unsurprising given the variety of cultural and religious patterns across this region. The most marked differences are in the legal and ethical stances towards assisted dying, although there are also variations in limitation of life-sustaining treatment and the authority of advance directives to decline such treatment. Palliative care has made a rapid and impressive development in many European countries over the last decade, and alleviating symptoms at the end of life is permitted, even if the drugs used might (in the rare case) not only relieve suffering but also shorten life. Fueled by the politically led process of European harmonization, future policies and laws on end-of-life care might converge. However, at the base of many ethical conflicts there remain deeply rooted differences about promoting the sanctity of life, eradicating suffering, and respecting patients' autonomous wishes.

The objective of this paper is to understand from a sociological perspective how the moral question of euthanasia, framed as the "right to die", emerges and is dealt with in society. It takes France and Germany as case studies, two countries in which euthanasia is prohibited and which have similar legislation on the issue. I presuppose that, and explore how, each society has its own specificities in terms of practical, social and political norms that affect the ways in which they deal with these issues. The paper thus seeks to understand how requests for the "right to die" emerge in each society, through both the debate (analysis of daily newspapers, medical and philosophical literature, legal texts) and the practices (ethnographic work in three French and two German hospitals) that elucidate the phenomenon. It does so, however, without attempting to solve the moral question of euthanasia. In spite of the differences observed between these two countries, the central issue at stake in their respective debates is the question of the individual's autonomy to choose the conditions in which he or she wishes to die; these conditions depend, amongst others, on the doctor-patient relationship, the organisation of end-of-life care in hospital settings, and more generally, on the way autonomy is defined and handled in the public debate.

Der vorliegende Artikel beschaftigt sich damit, warum die moralische Frage nach dem Selbstbestimmungsrecht des Todes zu einem bestimmten Zeitpunkt in einer Gesellschaft auftritt und wie sie behandelt wird. Dazu werden zwei Lander verglichen, in denen Sterbehilfe verboten ist, namlich Frankreich und Deutschland. Mit Hilfe einer Analyse der verschiedenen Debatten und Praktiken wird versucht, die Grunde fur Bitten nach Sterbehilfe besser zu verstehen, ohne jedoch das moralische Problem der Sterbehilfe losen zu wollen. In einem ersten Schritt wird auf die unterschiedlichen Bedeutungen des Begriffs der „Euthanasie“ im Wandel der Zeit hingewiesen und die unterschiedlichen sozialen, geschichtlichen und rechtlichen Hintergrunde der franzosischen und deutschen Debatte untersucht. Anschliesend werden die normativen Schwierigkeiten der Personen hinterfragt, die haufig mit Situationen am Lebensende konfrontiert sind, und in weiterem Sinne, die einer ganzen Gesellschaft. Es soll erfasst werden, warum manche Personen eine bestimmte Handlungsweise als „gut“ und andere sie als „schlecht“ beurteilen, und in wiefern diese Urteile sich durch soziale, historische, berufliche oder personliche Bedingungen erklaren lassen.

Background Advance decisions to refuse treatment (ADs) are widely discussed as important means to enhance patient autonomy at the end of life even where patients are no longer able to communicate themselves their will. The Council of Europe recommended twice that all member states should adopt legislation on ADs and some countries such as England, Germany, and France recognise legal value to ADs. Yet, in practice these documents are only infrequently implemented. Aim The paper aims to examine problems physicians from England, Germany, and France associate with regard to ADs, and more generally EOL decisions. The paper will show how the place accorded to patient preferences influences the potential role of ADs in ethics guidance and policies in the three countries. Methods 1. Literature review; 2. Four months of ethnographic direct observations in university hospitals in each country in neuro-oncology, neurology (ALS), and oncology; 3. Approx. 45 interviews with physicians in England, Germany, and France. Results and discussion The analysis reveals differences in the way patient preferences are taken into consideration in the legal context, in the public debate and professional guidelines, and by physicians. The paper shows how this influences physician’s attitudes towards end-of-life decisions in general, and more particularly towards ADs. Conclusion Understanding the differences between the physician-patient relationship in both countries helps to inform the kind of policy and ethical guidance that should be developed. It follows that a comparative approach of these countries is an important first step in developing comprehensive recommendations for the use of ADs.

Introduction: Although tuberculosis (TB) is the most common cause of mortality from infectious diseases worldwide, genitourinary TB in North America is rare. We review 3 cases of genitourinary TB diagnosed within the last 5 years.Cases: The first case is that of a 76-year-old African-Canadian woman who was referred for percutaneous nephrolithotomy of right lower pole renal stones. Although renal TB was suspected, her initial urinary TB culture was negative. On follow-up imaging, she developed bilateral ureteral thickening and ureteroscopic biopsy confirmed necrotizing granulomata. Repeat urine cultures were positive for M. tuberculosis. The second case is a 73-yearold Italian-Canadian woman who was referred for ureteroscopic biopsy of left thickened ureter to rule out urothelial carcinoma. Initial urine TB cultures were negative, despite biopsies confirming granulomatous inflammation. She was closely followed with urine cytologies and TB cultures. Repeat urine culture was positive for M. tuberculosis. Both patients were treated with a course of anti-tuberculous agents and indwelling ureteral stents to relieve ureteral obstruction. The third case is a 70-year-old Cree woman who was referred for percutaneous nephrolithotomy of a left “staghorn stone” in an atrophic left kidney. Thirty years earlier she had been treated for pulmonary TB in addition to ileocystoplasty for a “thimble” bladder. A computed tomography scan showed autonephrectomized left kidney. Her urine TB cultures were negative. She was placed on prophylactic antibiotics for her recurrent bacterial urinary tract infections.Conclusion: Genitourinary TB may present in various subtle ways, and the astute clinician must have a high index of suspicion for this disease in patients with atypical clinical and radiologic findings. In addition, TB urine cultures should be repeated when there is high index of suspicion.

The apoprotein of the major light-harvesting chlorophyll a/b complex (LHCIIb) is post-translationally imported into the chloroplast, where membrane insertion, protein folding, and pigment binding take place. The sequence and molecular mechanism of the latter steps is largely unknown. The complex spontaneously self-organises in vitro to form structurally authentic LHCIIb upon reconstituting the unfolded recombinant protein with the pigments chlorophyll a, b, and carotenoids in detergent micelles. Former measurements of LHCIIb assembly had revealed two apparent kinetic phases, a faster one (tau1) in the range of 10 s to 1 min, and a slower one (tau2) in the range of several min. To unravel the sequence of events we analysed the binding of chlorophylls into the complex by using time-resolved fluorescence measurements of resonance energy transfer from chlorophylls to an acceptor dye attached to the apoprotein. Chlorophyll a, offered in the absence of chlorophyll b, bound with the faster kinetics (tau1) exclusively whereas chlorophyll b, in the absence of chlorophyll a, bound predominantly with the slower kinetics (tau2). In double-jump experiments, LHCIIb assembly could be dissected into a faster chlorophyll a and a subsequent, predominantly slower chlorophyll b-binding step. The assignment of the faster and the slower kinetic phase to predominantly chlorophyll a and exclusively chlorophyll b binding, respectively, was verified by analysing the assembly kinetics with a circular dichroism signal in the visible domain presumably reflecting the establishment of pigment-pigment interactions. We propose that slow chlorophyll binding is confined to the exclusively chlorophyll b binding sites whereas faster binding occurs to the chlorophyll a binding sites. The latter sites can bind both chlorophylls a and b but in a reversible fashion as long as the complex is not stabilised by proper occupation of the chlorophyll b sites. The resulting two-step model of LHCIIb assembly is able to reconcile the highly specific binding sites containing either chlorophyll a or b, as seen in the recent crystal structures of LHCIIb, with the observation of promiscuous binding sites able to bind both chlorophyll a and b in numerous reconstitution analyses of LHCIIb assembly.