Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma

Metabolomics as one of the most rapidly growing technologies in the "-omics" field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Formula: see text] We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and-despite all its current limitations-can deliver marker panels with high selectivity even in multi-class settings.

Laryngeal and hypopharyngeal carcinomas after (chemo)radiotherapy: a diagnostic dilemma

PURPOSE OF REVIEW: During recent years, (chemo)radiotherapy has evolved into a primary treatment modality for both early and advanced laryngeal and hypopharyngeal carcinomas. Head and neck surgeons will be concerned more frequently with patients presenting symptoms and signs suggesting recurrent tumor or complications of (chemo)radiotherapy. RECENT FINDINGS: Analysis of histologic characteristics and tumor spread of recurrent carcinomas on whole-organ slices of salvage laryngectomy specimens showed that recurrent laryngeal carcinomas are often present with multiple tumor foci dispersed in different regions; furthermore, they may develop beneath an intact mucosa. Only a few articles analyze the reliability of laryngoscopy and biopsy in detecting recurrences after (chemo)radiotherapy: the number of false negative biopsies is relatively high. The differentiation between radionecrosis and tumor recurrence is difficult by computed tomography scan and magnetic resonance imaging in many cases. Positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging are promising diagnostic modalities to detect or exclude persistent or recurrent disease after (chemo)radiotherapy. SUMMARY: Endoscopy with biopsy, computed tomography scan and conventional magnetic resonance imaging present several deficiencies in diagnosing recurrent disease after (chemo)radiotherapy. New imaging modalities such as positron emission tomography-computed tomography and diffusion-weighted magnetic resonance imaging show promising results, increasing the diagnostic efficacy.

Orphanhood, Poverty and the Care Dilemma: Review of Global Policy Trends

The care and protection of children experiencing orphanhood presents a major child-care policy challenge. This paper draws on a review of the literature to document divergent conceptualizations of orphanhood, how the hurdles for the care of orphans reflect wider issues of poverty and inequality, as well as the ways in which different care interventions (familial, institutional, community-based and rights-based) might be appropriated for children in need. It is argued that the map of contemporary orphanhood overlaps with the contours of global poverty, inequality, age-based deprivations and marginalization. An example of a ‘globalised’ model of orphan care, namely SOS Children’s Villages, is presented and its implications for policy are examined. The paper highlights the significance of fighting poverty and enhancing the care-giving capabilities of extended families in the care and protection of children from a rights-based perspective. It suggests that external interventions should primarily address the structural causes of poverty and marginality, rather than amplifying inequalities through the selective support of orphans in economically vulnerable communities.

The Role of Ambidexterity in Marketing Strategy Implementation: Resolving the Exploration-Exploitation Dilemma

Formulating consistent marketing strategies is a difficult task, but successfully implementing them is even more challenging. This is even more pertinent as marketing strategies quite often incorporate inherent conflicts between major breakthroughs and consolidation. Consequently, marketers need to balance exploratory and exploitative strategies. However, the literature lacks concrete insights for marketing managers as to how exploratory and exploitative strategies can be best combined. This paper addresses this issue by introducing a framework of multiple types of ambidexterity. Based on qualitative research, tools and procedures are identified to overcome marketing dilemmas and support strategy implementation by drawing on ambidextrous designs.

Beyond the Pro and Contra of Evidence-Based Practice: Reflections on a Recurring Dilemma at the Core of Social Work

Currently, social work is witnessing a quite polarized debate about what should be the basis for good practice. Simply stated, the different attempts to define the required basis for effective and accountable interventions in social work practice can be grouped in two paradigmatic positions, which seem to be in strong opposition to each other. On the one hand the highly influential evidence based practice movement highlights the necessity to base practice interventions on proven effectiveness from empirical research. Despite some variations, such as between narrow conceptions of evidence based practice (see e.g. McNeece/Thyer, 2004) and broader approaches to it (see e.g. Gambrill, 1999, 2001, 2008), the evidence based practice movement embodies a positivist orientation and more explicitly scientific aspirations of social work by using positivistic empirical strategies. Critics of the evidence based practice movement argue that its narrow epistemological assumptions are not appropriate for the understanding of social phenomena and that evidence based guidelines to practice are insufficient to deal with the extremely complex activities social work practice requires in different and always somewhat unique practice situations (Webb, 2001; Gray & Mc Donald, 2006; Otto, Polutta &Ziegler, 2009). Furthermore critics of evidence based practice argue that it privileges an uncritical and a-political positivism which seems highly problematic in the current climate of welfare state reforms, in which the question ‘what works’ is highly politicized and the legitimacy of professional social work practice is being challenged maybe more than ever before (Kessl, 2009). Both opponents and proponents of evidence based practice argue on the epistemological, the methodological and the ethical level to sustain their point of view and raise fundamental questions about the real nature of social work practice, so that one could get the impression that social work is really at the crossroads between two very different conceptions of social work practice and its further professional development (Stepney, 2009). However, this article is not going to merely rehearse the pro and contra of different positions that are being invoked in the debate about evidence based practice. Instead it aims to go further by identifying the dilemmas underlying these positions which - so it is argued – re-emerge in the debate about evidence based practice, but which are older than this debate. They concern the fundamental ambivalence modern professionalization processes in social work were subjected to from their very beginnings.

Is there a ‚Depth versus Participation‘ Dilemma in International Cooperation?

Much of the International Relations literature assumes that there is a “depth versus participation” dilemma in international politics: shallower international agreements attract more countries and greater depth is associated with less participation. We argue that this conjecture is too simple and probably misleading because the depth of any given cooperative effort is in fact multidimensional. This multidimensionality manifests itself in the design characteristics of international agreements: in particular, the specificity of obligations, monitoring and enforcement mechanisms, dispute settlement mechanisms, positive incentives (assistance), and organizational structures (secretariats). We theorize that the first three of these design characteristics have negative and the latter three have positive effects on participation in international cooperative efforts. Our empirical testing of these claims relies on a dataset that covers more than 200 global environmental treaties. We find a participation-limiting effect for the specificity of obligations, but not for monitoring and enforcement. In contrast, we observe that assistance provisions in treaties have a significant and substantial positive effect on participation. Similarly, dispute settlement mechanisms tend to promote treaty participation. The main implication of our study is that countries do not appear to stay away from agreements with monitoring and enforcement provisions, but that the inclusion of positive incentives and dispute settlement mechanisms can promote international cooperation. In other words, our findings suggest that policymakers do not necessarily need to water down global treaties in order to obtain more participation.

Drittschuldners Dilemma

"Die alten Rechte, wie wir sie ererbt von unsern Vätern, wollen wir bewahren, nicht ungezügelt nach dem Neuen greifen" (Schiller). In Zeiten des Umbruchs, wie sie im Zivilprozess bevorstehen, gilt es, das Neue gekonnt mit dem Bewährten zu verweben. Der vorliegende Band vereinigt 27 Beiträge, die in freier Form den Dialog über aktuelle Fragen des Zivil-, Schiedsverfahrens- und Vollstreckungsrechts aufnehmen. Freunde, Bekannte und Fachkollegen gratulieren damit dem Mitverfasser des Kommentars zur Zivilprozessordnung für den Kanton Bern zum 65. Geburtstag.