Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with estrogen receptor-positive, HER-2-positive advanced breast cancer: a proof-of-concept trial (SAKK 23/03).

A sequential treatment design was chosen in this trial to ensure complete resistance to single-agent non-steroidal aromatase inhibitor (AI) and trastuzumab both given as monotherapy before receiving the combination of a non-steroidal AI and trastuzumab. Key eligibility criteria included postmenopausal patients with advanced, measurable, human epidermal growth factor receptor-2 (HER-2)-positive disease (assessed by FISH, ratio (≥2)), hormone receptor (HR)-positive disease, and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in the adjuvant or in the advanced setting. Patients received standard dose trastuzumab monotherapy in step 1 and upon disease progression continued trastuzumab in combination with letrozole in step 2. The primary endpoint was clinical benefit rate (CBR) in step 2. Totally, 13 patients were enrolled. In step 1, six patients (46%) achieved CBR. Median time to progression (TTP) was 161 days (95% confidence interval (CI): 82-281). In step 2, CBR was observed in eight out of the 11 evaluable patients (73%), including one patient with partial response. Median TTP for all the 11 patients was 188 days (95% CI: 77-not reached). Results of this proof-of-concept trial suggest that complete resistance to both AI and trastuzumab can be overcome in a proportion of patients by combined treatment of AI and trastuzumab, as all patients served as their own control. Our results appear promising for a new treatment strategy that offers a chemotherapy-free option for at least a subset of patients with HR-positive, HER-2-positive breast cancer over a clinically relevant time period.

Sumak Kawsay, or the concept of living well, and perceptions about natural, urban and rural areas: the case of Cuenca (Ecuador)

This research explores critical environmental concepts from the standpoint of political ecology. It contrasts the Ecuadorian Kichua indigenous concept of Sumak Kawsay (i.e., living well), with discourses about natural, urban and rural areas. Sumak Kawsay was included in Ecuador’s 2008 constitution as an alternative to the neoclassical idea of development. This work reveals interesting insights from a variety of social and political viewpoints from both rural and urban areas. The research is based on the medium sized city of Cuenca, which is located in the southern Ecuadorian Andes. We used an adaptation of the Q Method to investigate stakeholders’ perceptions. Four remarkably well-defined viewpoints were revealed. Although these views contrast strongly with Sumak Kawsay, it is possible to transform this paradigm in the foundation of Cuenca’s public policies and institutional structure.

Transitoriness - a concept

Background: The realization of life's transitory nature, i.e., 'transitoriness', is an experience that patients who arediagnosed with cancer may have. Transitoriness constitutesa challenging situation for cancer patients, theirrelatives, and healthcare professionals. Although issuesregarding life's finitude and associated outcomes havebeen described in related concepts such as deathawareness, the concept of transitoriness remains vague.This paper will present attributes, outcomes, and antecedentsof this concept.Review methods: Rodgers' (2000) evolutionary conceptanalysis was utilized to explore the concept of 'transitoriness',which requires the review of at least 20% of theidentified relevant publications. A total of 239 articles wereidentified as being relevant. Of this total number, 27% (66articles) were selected, reviewed and analyzed.Findings: Three main themes emerged that describe theconcept of 'transitoriness'. They were 'awareness oflife's finitude', 'anxiety' and 'change'. On the one hand,the confrontation with life's finitude provokes existentialfear and anxiety in the person. On the other hand,persons have the possibility of re-assessing their lifesituation. Thus, they can identify and explore newavenues for coping.Conclusion and clinical relevance: The identification ofthe attributes of 'transitoriness', i.e., awareness, anxiety,and change, will help clinicians to better understand cancerpatients' experience of their illness situation. It will also bepossible to better support cancer patients in their copingprocess. Research that can foster the development ofinterventions that can enhance patients' healthcare experiencewill be promoted.

Identification concept and the use of probabilities in forensic odontology--an approach by philosophical discussion.

This paper questions the practitioners' deterministic approach(es) in forensic identification and notes the limits of their conclusions in order to encourage a discussion to question current practices. With this end in view, a hypothetical discussion between an expert in dentistry and an enthusiastic member of a jury, eager to understand the scientific principles of evidence interpretation, is presented. This discussion will lead us to regard any argument aiming at identification as probabilistic.

Transapical aortic valve implantation without angiography: proof of concept.

Background: Cardiac computed tomographic scans, coronary angiograms, and aortographies are routinely performed in transcatheter heart valve therapies. Consequently, all patients are exposed to multiple contrast injections with a following risk of nephrotoxicity and postoperative renal failure. The transapical aortic valve implantation without angiography can prevent contrast-related complications. Methods: Between November 2008 and November 2009, 30 consecutive high-risk patients (16 female, 53.3%) underwent transapical aortic valve implantation without angiography. The landmarks identification, the stent-valve positioning, and the postoperative control were routinely performed under transesophageal echocardiogram and fluoroscopic visualization without contrast injections. Results: Mean age was 80.1 +/- 8.7 years. Mean valve gradient, aortic orifice area, and ejection fraction were 60.3 +/- 20.9 mm Hg, 0.7 +/- 0.16 cm(2), and 0.526 +/- 0.128, respectively. Risk factors were pulmonary hypertension (60%), peripheral vascular disease (70%), chronic pulmonary disease (50%), previous cardiac surgery (13.3%), and chronic renal insufficiency (40%) (mean blood creatinine and urea levels: 96.8 +/- 54 mu g/dL and 8.45 +/- 5.15 mmol/L). Average European System for Cardiac Operative Risk Evaluation was 32.2 +/- 13.3%. Valve deployment in the ideal landing zone was 96.7% successful and valve embolization occurred once. Thirty-day mortality was 10% (3 patients). Causes of death were the following: intraoperative ventricular rupture (conversion to sternotomy), right ventricular failure, and bilateral pneumonia. Stroke occurred in one patient at postoperative day 9. Renal failure (postoperative mean blood creatinine and urea levels: 91.1 +/- 66.8 mu g/dL and 7.27 +/- 3.45 mmol/L), myocardial infarction, and atrioventricular block were not detected. Conclusions: Transapical aortic valve implantation without angiography requires a short learning curve and can be performed routinely by experienced teams. Our report confirms that this procedure is feasible and safe, and provides good results with low incidence of postoperative renal disorders. (Ann Thorac Surg 2010; 89: 1925-33) (C) 2010 by The Society of Thoracic Surgeons

Spheres of diversities: from concept to policy

This book is concerned with the diversity debate in the context of Europe.It is about diversity both as a concept and as a policy. Indeed, the epicentreof the analysis is the link between the spheres of diversity-concepts anddiversity-policies. The book explores how the concept of diversity orientatespolicies and management, and also how public/private managementfacilitates new policy orientations. As such, the book enhances conceptualthinking on diversity, but also facilitates policy thinking on the conceptinvolved in novel policy orientations towards diversity.

Immunoscintigraphic localization of inflammatory lesions: concept, radiolabelling and in vitro testing of a granulocyte specific antibody.

Current nuclear medicine techniques for the localization of inflammatory processes are based on injection of 111In labelled autologous granulocytes which need to be isolated and radiolabelled in vitro before reinjection. A new technique is presented here that obviates the need for cell isolation by the direct intravenous injection of a granulocyte specific 123I labelled monoclonal antibody. In this publication the basic parameters of the antibody granulocyte interaction are described. Antibody binding does not inhibit vital functions of the granulocytes, such as chemotaxis and superoxide generation. Scatchard analysis of binding data reveals an apparent affinity of the antibody for granulocytes of 6.8 X 10(9) l/mol and approximately 7.1 X 10(4) binding sites per cell. Due to the high specificity of the antibody, the only expected interference is from CEA producing tumors.

Property as an economic concept: Reconciling legal and economic conceptions of property rights in a Coasean framework

Adopting a simplistic view of Coase (1960), most economic analyses of property rightsdisregard both the key advantage that legal property rights (that is, in rem rights) provide torightholders in terms of enhanced enforcement, and the difficulties they pose to acquirers interms of information asymmetry about legal title. Consequently, these analyses tend to overstatethe role of "private ordering" and disregard the two key elements of property law: first, theessential conflict between property (that is, in rem) enforcement and transaction costs; and,second, the institutional solutions created to overcome it, mainly contractual registries capable ofmaking truly impersonal (that is, asset-based) trade viable when previous relevant transactionson the same assets are not verifiable by judges. This paper fills this gap by reinterpreting bothelements within the Coasean framework and thus redrawing the institutional foundations of bothproperty and corporate contracting.