Exploring the compassion deficit debate.

Several recent high profile failures in the UK health care system have promoted strong debate on compassion and care in nursing. A number of papers articulating a range of positions within this debate have been published in this journal over the past two and a half years. These articulate a diverse range of theoretical perspectives and have been drawn together here in an attempt to bring some coherence to the debate and provide an overview of the key arguments and positions taken by those involved. In doing this we invite the reader to consider their own position in relation to the issues raised and to consider the impact of this for their own practice. Finally the paper offers some sense of how individual practitioners might use their understanding of the debates to ensure delivery of good nursing care.

Effect of a COL1A1 Sp1 Binding Site Polymorphism on Arterial Pulse Wave Velocity: An Index of Compliance.

Reduced arterial compliance precedes changes in blood pressure, which may be mediated through alterations in vessel wall matrix composition. We investigated the effect of the collagen type I-1 gene (COL1A1) +2046G>T polymorphism on arterial compliance in healthy individuals. We recruited 489 subjects (251 men and 238 women; mean age, 22.6±1.6 years). COL1A1 genotypes were determined using polymerase chain reaction and digestion by restriction enzyme Bal1. Arterial pulse wave velocities were measured in 3 segments, aortoiliac (PWVA), aortoradial (PWVB), and aorto-dorsalis-pedis (PWVF), as an index of compliance using a noninvasive optical method. Data were available for 455 subjects. The sample was in Hardy-Weinberg equilibrium with genotype distributions and allele frequencies that were not significantly different from those reported previously. The T allele frequency was 0.22 (95% confidence interval, 0.19 to 0.24). Two hundred eighty-three (62.2%) subjects were genotype GG, 148 (35.5%) subjects were genotype GT, and 24 (5.3%) subjects were genotype TT. A comparison of GG homozygotes with GT and TT individuals demonstrated a statistically significant association with arterial compliance: PWVF 4.92±0.03 versus 5.06±0.05 m/s (ANOVA, P=0.009), PWVB 4.20±0.03 versus 4.32±0.04 m/s (ANOVA, P=0.036), and PWVA 3.07±0.03 versus 3.15±0.03 m/s (ANOVA, P=0.045). The effects of genotype were independent of age, gender, smoking, mean arterial pressure, body mass index, family history of hypertension, and activity scores. We report an association between the COL1A1 gene polymorphism and arterial compliance. Alterations in arterial collagen type 1A deposition may play a role in the regulation of arterial compliance

WASP-1b and WASP-2b: Two new transiting exoplanets detected with SuperWASP and SOPHIE

We have detected low-amplitude radial-velocity variations in two stars, USNO-B1.0 1219-0005465 (GSC 02265-00107 = WASP-1) and USNO-B1.0 0964-0543604 (GSC 00522-01199 = WASP-2). Both stars were identified as being likely host stars of transiting exoplanets in the 2004 SuperWASP wide-field transit survey. Using the newly commissioned radial-velocity spectrograph SOPHIE at the Observatoire de Haute-Provence, we found that both objects exhibit reflex orbital radial-velocity variations with amplitudes characteristic of planetary-mass companions and in-phase with the photometric orbits. Line-bisector studies rule out faint blended binaries as the cause of either the radial-velocity variations or the transits. We perform preliminary spectral analyses of the host stars, which together with their radial-velocity variations and fits to the transit light curves yield estimates of the planetary masses and radii. WASP-1b and WASP-2b have orbital periods of 2.52 and 2.15 d, respectively. Given mass estimates for their F7V and K1V primaries, we derive planet masses 0.80-0.98 and 0.81-0.95 times that of Jupiter, respectively. WASP-1b appears to have an inflated radius of at least 1.33 RJup, whereas WASP-2b has a radius in the range 0.65-1.26 RJup.

Enrichment and analysis of nonenzymatically glycated peptides: Boronate affinity chromatography coupled with electron-transfer dissociation mass spectrometry

Nonenzymatic glycation of peptides and proteins by D-glucose has important implications in the pathogenesis of diabetes mellitus, particularly in the development of diabetic complications. However, no effective high-throughput methods exist for identifying proteins containing this low-abundance posttranslational modification in bottom-up proteomic studies. In this report, phenylboronate affinity chromatography was used in a two-step enrichment scheme to selectively isolate first glycated proteins and then glycated, tryptic peptides from human serum glycated in vitro. Enriched peptides were subsequently analyzed by alternating electron-transfer dissociation (ETD) and collision induced dissociation ( CID) tandem mass spectrometry. ETD fragmentation mode permitted identification of a significantly higher number of glycated peptides (87.6% of all identified peptides) versus CID mode (17.0% of all identified peptides), when utilizing enrichment on first the protein and then the peptide level. This study illustrates that phenylboronate affinity chromatography coupled with LC-MS/MS and using ETD as the fragmentation mode is an efficient approach for analysis of glycated proteins and may have broad application in studies of diabetes mellitus.

A role of cellular prion protein in programming T-cell cytokine responses in disease.

The cellular prion protein (PrPC) is widely expressed in neural and non-neural tissues, but its function is unknown. Elucidation of the part played by PrPC in adaptive immunity has been a particular conundrum: increased expression of cell surface PrPC has been documented during T-cell activation, yet the functional significance of this activation remains unclear, with conflicting data on the effects of Prnp gene knockout on various parameters of T-cell immunity. We show here that Prnp mRNA is highly inducible within 8–24 h of T-cell activation, with surface protein levels rising from 24 h. When measured in parallel with CD69 and CD25, PrPC is a late activation antigen. Consistent with its up-regulation being a late activation event, PrP deletion did not alter T-cell-antigen presenting cell conjugate formation. Most important, activated PrP0/0 T cells demonstrated much reduced induction of several T helper (Th) 1, Th2, and Th17 cytokines, whereas others, such as TNF- and IL-9, were unaffected. These changes were investigated in the context of an autoimmune model and a bacterial challenge model. In experimental autoimmune encephalomyelitis, PrP-knockout mice showed enhanced disease in the face of reduced IL-17 responses. In a streptococcal sepsis model, this constrained cytokine program was associated with poorer local control of infection, although with reduced bacteremia. The findings indicate that PrPC is a potentially important molecule influencing T-cell activation and effector function.

El significado de la prosopopeya de las Leyes en el "Critón" de Platon

El objeto de este trabajo es realizar un estudio iusfilosófico sobre la aparición de las Leyes (nómoi) personificadas de Atenas en el Critón de Platón. La prosopopeya de las Leyes resulta ser un aspecto central para poder comprender la obra, ya que éstas entablan un diálogo imaginario con Sócrates en el cual instalan diversos argumentos filosóficos para fundamentar la autoridad de la pólis. A los fines de identificar el valor argumentativo de este recurso en la obra, analizaré el significado del nómos en la Atenas del siglo V a. C. y la naturaleza de las Leyes en el contexto general del diálogo. Se busca demostrar la importancia que tienen aquéllas para explicar la decisión de Sócrates de beber la cicuta.

A timing-specific memory distortion effect in young children

It has been suggested that there are systematic distortions in children's memory for temporal durations, such that children's memory is not just less accurate than that of adults but qualitatively different. Experiment I replicated the memory distortion effect by demonstrating developmental change in the tendency to confuse a reference duration with one that is shorter rather than longer than it. When the long-term memory demands of the task were reduced by providing reminders of the reference duration on every trial, there were no such qualitative changes in error patterns (Experiment 2). Further evidence for developmental changes in memory distortion was found in the temporal generalization task of Experiment 3, in which stimuli were spaced logarithmically rather than linearly. In Experiment 4, a similar distortion pattern was absent in a task in which children made judgments about the pitch rather than the duration of stimuli, suggesting the effect may be specific to time estimation. (C) 2003 Elsevier Inc. All rights reserved.

Concordant Association of Insulin Degrading Enzyme Gene (IDE) Variants with IDE mRNA, A beta, and Alzheimer's Disease

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD).

Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 x 10(-9)) and 5. to the PICALM gene (rs3851179, P = 1.9 x 10(-8)). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86).

Season and outdoor ambient temperature: Effects on birth weight

Objective: To determine the extent to which meteorologic factors explain seasonality in birth weight in a developed country.

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.