Reasons why people in Switzerland seek assisted suicide : the view of patients and physicians

Background: Assisted suicide is permitted in Switzerland provided that assistance is not motivated by selfish reasons. Suicides are commonly performed with the assistance of right-to-die organisations and the use of a lethal dose of barbiturates prescribed by a participating physician. We examined the reasons physicians provided for writing the prescription and the reasons patients gave for requesting assistance in dying. Methods: We analysed all reported cases of assisted suicide that were facilitated by right-to-die organisations between 2001 and 2004 in the city of Zurich, and for which both the medical report and the optional letter written by the decedent providing information on their reasons for seeking assistance in suicide (N = 165). Results: The reasons most often reported by physicians (ph), as well as persons who sought help (p), were: pain (ph: 56% of all assisted suicides, p: 58%), need for long-term care (ph: 37%, p: 39%), neurological symptoms (ph: 35%, p: 32%), immobility (ph: 23%, p: 30%) and dyspnoea (ph: 23%, p: 23%). Control of circumstances over death (ph: 12%, p: 39%); loss of dignity (ph: 6%, p: 38%); weakness (ph: 13%, p: 26%); less able to engage in activities that make life enjoyable (ph: 6%, p: 18%); and insomnia and loss of concentration (ph: 4%, p: 13%) were significantly more often mentioned by decedents than by physicians. Conclusions: Both prescribing physicians and;patients provided with assistance to die quite often mentioned pain and other concerns, many of which were objectively assessable and related to unbearable suffering or unreasonable disability. Concerns referable to autonomy and individual judgement were more often noted by people seeking help than by the prescribing physicians

A Gamma-convergence argument for the blow-up of a non-local semilinear parabolic equation with Neumann boundary conditions

In this paper we study a simple non-local semilinear parabolic equation with Neumann boundary condition. We give local existence result and prove global existence for small initial data. A natural non increasing in time energy is associated to this equation. We prove that the solution blows up at finite time $T$ if and only if its energy is negative at some time before $T$. The proof of this result is based on a Gamma-convergence technique

Yarn diameter characterization using two orthogonal directions

We have used a coherent optical signal processing technique based on Fourier optics to characterize yarn diameter using a single projection.Fundação para a Ciência e a Tecnologia (FCT) - BD/19028/200

Normal subgroups in the Cremona group (long version)

Let k be an algebraically closed field. We show that the Cremona group of all birational transformations of the projective plane P^2 over k is not a simple group. The strategy makes use of hyperbolic geometry, geometric group theory, and algebraic geometry to produce elements in the Cremona group that generate non trivial normal subgroups.Comment: With an appendix by Yves de Cornulier. Numerous but minors corrections were made, regarding proofs, references and terminology. This long version contains detailled proofs of several technical lemmas about hyperbolic space

Performance Analysis of Orthogonal Pairs Designed for an Expanded Eukaryotic Genetic Code

Background: The suppression of amber stop codons with non-canonical amino acids (ncAAs) is used for the site-specific introduction of many unusual functions into proteins. Specific orthogonal aminoacyl-tRNA synthetase (o-aaRS)/amber suppressor tRNA CUA pairs (o-pairs) for the incorporation of ncAAs in S. cerevisiae were previously selected from an E. coli tyrosyl-tRNA synthetase/tRNACUA mutant library. Incorporation fidelity relies on the specificity of the o-aaRSs for their ncAAs and the ability to effectively discriminate against their natural substrate Tyr or any other canonical amino acid. Methodology/Principal Findings: We used o-pairs previously developed for ncAAs carrying reactive alkyne-, azido-, or photocrosslinker side chains to suppress an amber mutant of human superoxide dismutase 1 in S. cerevisiae. We found worse incorporation efficiencies of the alkyne- and the photocrosslinker ncAAs than reported earlier. In our hands, amber suppression with the ncAA containing the azido group did not occur at all. In addition to the incorporation experiments in S. cerevisiae, we analyzed the catalytic properties of the o-aaRSs in vitro. Surprisingly, all o-aaRSs showed much higher preference for their natural substrate Tyr than for any of the tested ncAAs. While it is unclear why efficiently recognized Tyr is not inserted at amber codons, we speculate that metabolically inert ncAAs accumulate in the cell, and for this reason they are incorporated despite being weak substrates for the o-aaRSs. Conclusions/Significance: O-pairs have been developed for a whole plethora of ncAAs. However, a systematic and detaile

The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia

Expression of the MECOM (also known as EVI1) proto-oncogene is deregulated by chromosomal translocations in some cases of acute myeloid leukemia (AML) and is associated with poor clinical outcome. Here, through transcriptomic and metabolomic profiling of hematopoietic cells, we reveal that EVI1 overexpression alters cellular metabolism. A screen using pooled short hairpin RNAs (shRNAs) identified the ATP-buffering, mitochondrial creatine kinase CKMT1 as necessary for survival of EVI1-expressing cells in subjects with EVI1-positive AML. EVI1 promotes CKMT1 expression by repressing the myeloid differentiation regulator RUNX1. Suppression of arginine-creatine metabolism by CKMT1-directed shRNAs or by the small molecule cyclocreatine selectively decreased the viability, promoted the cell cycle arrest and apoptosis of human EVI1-positive cell lines, and prolonged survival in both orthotopic xenograft models and mouse models of primary AML. CKMT1 inhibition altered mitochondrial respiration and ATP production, an effect that was abrogated by phosphocreatine-mediated reactivation of the arginine-creatine pathway. Targeting CKMT1 is thus a promising therapeutic strategy for this EVI1-driven AML subtype that is highly resistant to current treatment regimens. Keywords: AML; RUNX1; CKMT1; cyclocreatine; arginine metabolismNational Cancer Institute (U.S.) (NIH 1R35 CA210030-01)Stand Up To CancerBridge ProjectNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051

The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier