Don\'t Ask, Don\'t Tell: Ethical Issues Concerning Learning and Maintaining Life-Saving Skills

Undergraduate and postgraduate medical education entails acquiring and maintaining technical skills of various natures. Peripheral venous cannulation, splinting of fracture, wound suturing, venous cut-down and intra-osseous catheter placement for the most part, are considered minimally invasive procedures. The traditional way of skill acquisition could be summarised by the adage “See one, do one, teach one”. Although the saying may be a misrepresentation of the reality, it should not be an optional educational approach. Patients undergoing a procedure under general anaesthesia are often not informed of the possibility that they could be used for “ghost procedures”- part or whole of the procedure is performed by a trainee. An attitude of “don't ask, don't tell” devalues patients' autonomy and the trainee's moral integrity. In view of the polarisation of the views about teaching, acquiring, and maintaining technical skills, institutions should consider and deliberate on these principles and reach consensus on a set of guidelines to clarify and limit the practice of learning technical skills on patients and on the newly dead. Informed consent procedures and requirements must be clearly established and communicated. The learning and proficiency practices should be restricted to the staff that can truly benefit from the experience. The practice of ‘don't ask, don't tell' is not an option. South African Journal of Family Practice Vol. 50 (4) 2008: pp. 52-5

Patients’ use of information about medicine side effects in relation to experiences of suspected adverse drug reactions

Background Adverse drug reactions (ADRs) are common, and information about medicines is increasingly widely available to the public. However, relatively little work has explored how people use medicines information to help them assess symptoms that may be suspected ADRs. Objective Our objective was to determine how patients use patient information leaflets (PILs) or other medicines information sources and whether information use differs depending on experiences of suspected ADRs. Method This was a cross-sectional survey conducted in six National Health Service (NHS) hospitals in North West England involving medical in-patients taking at least two regular medicines prior to admission. The survey was administered via a questionnaire and covered use of the PIL and other medicines information sources, perceived knowledge about medicines risks/ADRs, experiences of suspected ADRs, plus demographic information. Results Of the 1,218 respondents to the survey, 18.8 % never read the PIL, whilst 6.5 % only do so if something unexpected happens. Educational level was related to perceived knowledge about medicines risks, but not to reading the PIL or seeking further information about medicines risks. Over half the respondents (56.0 %) never sought more information about possible side effects of medicines. A total of 57.2 % claimed they had experienced a suspected ADR. Of these 85.9 % were either very sure or fairly sure this was a reaction to a medicine. Over half of those experiencing a suspected ADR (53.8 %) had read the PIL, of whom 36.2 % did so before the suspected ADR occurred, the remainder afterwards. Reading the PIL helped 84.8 % of these respondents to decide they had experienced an ADR. Educational level, general knowledge of medicines risks and number of regular medicines used all increased the likelihood of experiencing an ADR. Conclusion More patients should be encouraged to read the PIL supplied with medicines. The results support the view that most patients feel knowledgeable about medicines risks and suspected ADRs and value information about side effects, but that reading about side effects in PILs or other medicines information sources does not lead to experiences of suspected ADRs

Baryon charge from embedding topology and a continuous meson spectrum in a new holographic gauge theory

We study a new holographic gauge theory based on probe D4-branes in the background dual to D4-branes on a circle with antiperiodic boundary conditions for fermions. Field theory configurations with baryons correspond to smooth embeddings of the probe D4-branes with nontrivial winding around an S^4 in the geometry. As a consequence, physics of baryons and nuclei can be studied reliably in this model using the abelian Born-Infeld action. However, surprisingly, we find that the meson spectrum is not discrete. This is related to a curious result that the action governing small fluctuations of the gauge field on the probe brane is the five-dimensional Maxwell action in Minkowski space despite the non-trivial embedding of the probe brane in the curved background geometry.Comment: 24 pages, LaTeX, 10 figures, v4: previously ignored effects of coupling to RR-fields included, meson spectrum qualitatively changed, v5: journal versio

Micromechanics of the growth of a craze fibril in glassy polymers

The primary objective of this work is to model the growth and eventual failure of a craze fibril in a classy polymer, starting from a primitive fibril. Experimental investigations have shown that properties like the entanglement density of a polymer play a pivotal role in determining whether macroscopic failure of a polymer occurs through crazing or shear yielding. Failure is seen to be related to the formation of a soft 'active zone' at the craze-bulk interface. through disentanglement. The present work aims at explaining some of the experimental findings about fibril growth and failure in glassy polymers on the basis of a continuum model of a craze with a constitutive model that accounts for yield, network hardening and disentanglement. The results show that this approach is capable of providing explanations for experimentally observed facts such as the propensity to crazing in polymers with low entanglement density and the linearity between the stretch in a fibril and the maximum stretch of a molecular strand in the fibril. (c) 2005 Elsevier Ltd. All rights reserved

Effectiveness of preoperative planning in the restoration of balance and view in ankylosing spondylitis

Object. The object of this study was to assess the effectiveness of preoperative planning in the restoration of balance and view angle in patients treated with lumbar osteotomy in ankylosing spondylitis (AS). Methods. The authors prospectively analyzed 8 patients with a thoracolumbar kyphotic deformity due to AS that was treated using a closing wedge osteotomy (CWO) of the lumbar spine to correct sagittal imbalance and horizontal view. Preoperative planning to predict postoperative balance, defined by the sagittal vertical axis (SVA) and the sacral endplate angle (SEA), and the view angle, defined by the chin-brow to vertical angle (CBVA), was performed using the ASKyphoptan computational program. Results. All patients were treated with a CWO at level L-4 and improved in balance and view angle. The mean correction angle was 35° (range 24-47°). The postoperative SEA improved from 21 to 36° for a mean correction of 15°. In addition, the SVA and CBVA improved significantly. Note, however, that the postoperative results did not exactly reflect the predicted values of the analyzed parameters. Conclusions. Preoperative planning for the restoration of balance and view angle in AS improves understanding of the biomechanical and clinical effects of a correction osteotomy of the lumbar spine. The adaptation of basic clinical and biomechanical principles to restore balance is advised in such a way that the individual SEA is corrected by 15° (maximum 40°) in relation to the horizon and C-7 is balanced exactly above the posterosuperior corner of the sacrum

Imaging transverse electron focusing in semiconducting heterostructures with spin-orbit coupling

Transverse electron focusing in two-dimensional electron gases (2DEGs) with strong spin-orbit coupling is revisited. The transverse focusing is related to the transmission between two contacts at the edge of a 2DEG when a perpendicular magnetic field is applied. Scanning probe microscopy imaging techniques can be used to study the electron flow in these systems. Using numerical techniques we simulate the images that could be obtained in such experiments. We show that hybrid edge states can be imaged and that the outgoing flux can be polarized if the microscope tip probe is placed in specific positions.Comment: Contribution to the Book/Proceedings of the PITP Les Houches School on "Quantum Magnetism" held on June, 2006. Final forma

ASKyphoplan: a program for deformity planning in ankylosing spondylitis

A closing wedge osteotomy of the lumbar spine may be considered to correct posture and spinal balance in progressive thoracolumbar kyphotic deformity caused by ankylosing spondylitis (AS). Adequate deformity planning is essential for reliable prediction of the effect of surgical correction of the spine on the sagittal balance and horizontal gaze of the patient. The effect of a spinal osteotomy on the horizontal gaze is equal to the osteotomy angle. However, the effect of a spinal osteotomy on the sagittal balance depends on both the correction angle and the level of osteotomy simultaneously. The relation between the correction angle, the level of osteotomy and the sagittal balance of the spine can be expressed by a mathematical equation. However, this mathematical equation is not easily used in daily practice. We present the computer program ASKyphoplan that analyses and visualizes the planning procedure for sagittal plane corrective osteotomies of the spine in AS. The relationship between the planned correction angle, level of osteotomy and sagittal balance are coupled into the program. The steps taken during an ASKyphoplan run are outlined, and the clinical application is discussed. The application of the program is illustrated by the analysis of the data from a patient recently treated by a lumbar osteotomy in AS. The software can be used free of charge on the internet at http://www.stega.nl under the heading “research” in the menu

Genes Involved in the Metabolism of Poly-Unsaturated Fatty-Acids (PUFA) and Risk for Crohn's Disease in Children & Young Adults

Epidemiological evidence for the role of polyunsaturated fatty-acids (PUFA) in Crohn's disease (CD) is unclear, although the key metabolite leucotriene B4 (LTB(4)) is closely linked to the inflammatory process. We hypothesized that inherited variation in key PUFA metabolic enzymes may modify susceptibility for CD.A case-control design was implemented at three pediatric gastroenterology clinics in Canada. Children ≤20 yrs diagnosed with CD and controls were recruited. 19 single nucleotide polymorphisms (SNPs) across the ALOX5 (4) CYP4F3 (5) and CYP4F2 (10) genes, were genotyped. Associations between SNPs/haplotypes and CD were examined. A total of 431 cases and 507 controls were studied. The mean (±SD) age of the cases was 12.4 (±3.3) years. Most cases were male (56.4%), had ileo-colonic disease (L3±L4, 52.7%) and inflammatory behavior (B1±p, 87%) at diagnosis. One genotyped CYP4F3 SNP (rs2683037) not in Hardy-Weinberg Equilibrium was excluded. No associations with the remaining 4 CYP4F3 SNPs with CD were evident. However haplotype analysis revealed associations with a two-marker haplotype (TG) (rs3794987 & rs1290617) (p = 0.02; permuted p = 0.08). CYP4F2 SNPs, rs3093158 (OR (recessive) = 0.56, 95% CI = 0.35-0.89; p = 0.01), rs2074902 (OR (trend) = 1.26, 95% CI = 1.00-1.60; p = 0.05), and rs2108622 (OR (recessive) = 1.6, 95% CI = 1.00-2.57; p = 0.05) were significantly associated whereas rs1272 (OR (recessive) = 0.58, 95% CI = 0.30-1.13; p = 0.10) showed suggestions for associations with CD. A haplotype comprising these 4 SNPs was significantly associated (p = 0.007, permuted p = 0.02) with CD. Associations with SNP rs3780901 in the ALOX5 gene were borderline non-significant (OR (dominant) = 1.29, 95% CI = 0.99-1.67; p = 0.056). A haplotype comprising the 4 ALOX5 SNPs (TCAA, p = 0.036) was associated with CD, but did not withstand corrections for multiple comparisons (permuted p = 0.14).Inherited variation in enzymes involved in the synthesis/metabolism of LTB(4) may be associated with CD. These findings implicate PUFA metabolism as a important pathway in the CD pathogenesis

Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

Background The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients. Objectives To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis. Results The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein-Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo. Conclusions Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant

NF-κB activation in inflammatory breast cancer is associated with oestrogen receptor downregulation, secondary to EGFR and/or ErbB2 overexpression and MAPK hyperactivation

Activation of NF-κB in inflammatory breast cancer (IBC) is associated with loss of estrogen receptor (ER) expression, indicating a potential crosstalk between NF-κB and ER. In this study, we examined the activation of NF-κB in IBC and non-IBC with respect to ER and EGFR and/or ErbB2 expression and MAPK hyperactivation. A qRT–PCR based ER signature was evaluated in tumours with and without transcriptionally active NF-κB, as well as correlated with the expression of eight NF-κB target genes. Using a combined ER/NF-κB signature, hierarchical clustering was executed. Hyperactivation of MAPK was investigated using a recently described MAPK signature (Creighton et al, 2006), and was linked to tumour phenotype, ER and EGFR and/or ErbB2 overexpression. The expression of most ER-modulated genes was significantly elevated in breast tumours without transcriptionally active NF-κB. In addition, the expression of most ER-modulated genes was significantly anticorrelated with the expression of most NF-κB target genes, indicating an inverse correlation between ER and NF-κB activation. Clustering using the combined ER and NF-κB signature revealed one cluster mainly characterised by low NF-κB target gene expression and a second one with elevated NF-κB target gene expression. The first cluster was mainly characterised by non-IBC specimens and IHC ER+ breast tumours (13 out of 18 and 15 out of 18 respectively), whereas the second cluster was mainly characterised by IBC specimens and IHC ER− breast tumours (12 out of 19 and 15 out of 19 respectively) (Pearson χ2, P<0.0001 and P<0.0001 respectively). Hyperactivation of MAPK was associated with both ER status and tumour phenotype by unsupervised hierarchical clustering using the MAPK signature and was significantly reflected by overexpression of EGFR and/or ErbB2. NF-κB activation is linked to loss of ER expression and activation in IBC and in breast cancer in general. The inverse correlation between NF-κB activation and ER activation is due to EGFR and/or ErbB2 overexpression, resulting in NF-κB activation and ER downregulation