Virtues in Competency-Based Assessment Frameworks: A Text Analysis.

Introduction: Official documentation of specialty training provides comprehensive and elaborate criteria to assess residents. These criteria are commonly described in terms of competency roles and entrustable professional activities (EPA's), but they may also implicitly encompass virtues. Virtues are desirable personal qualities that enable a person, in this case, a medical specialist, to make and act on the right decisions. We articulate these virtues and explore the resulting implied ideal of a medical professional. Method: We applied a two-staged virtue ethical content analysis to analyze documents, specific to the Dutch training program of the Ear, Nose, and Throat (ENT) specialty. First, we identified explicit references to virtues. Next, we articulated implicit virtues through interpretation. The results were categorized into cardinal, intellectual, moral, and professional virtues. Results: Thirty virtues were identified in the ENT- training program. Amongst them, practical wisdom, temperance, and commitment. Furthermore, integrity, curiosity, flexibility, attentiveness, trustworthiness and calmness are often implicitly assumed. Notable findings are the emphasis on efficiency and effectiveness. Together, these virtues depict an ideal of a future medical specialist. Conclusion: Our findings suggest that competency-frameworks and EPA's implicitly appeal to virtues and articulate a specific ideal surgeon. Explicit attention for virtue development and discussion of the role and relevance of implied ideal professionals in terms of virtues could further improve specialty training.

Wish-fulfilling medicine and wish-fulfilling dentistry.

OBJECTIVES: to explain the practice of wish-fulfilling medicine and how it relates to dentistry. SOURCES: Relevant papers, and reports from authoritative institutions were identified in Pubmed and Google Scholar. RESULTS: Wish-fulfilling medicine refers to services provided by professionals using medical methods in a medical setting to address non-medical wishes of patients. Care-providers, medical industries, and health-insurance companies also contribute to wish-fulfilling in medicine and dentistry. Various concepts of health and illness compounded by blurred borders between health and illness offer an unstable foundation for wish-fulfilling medicine, and growing demands for these services where healthcare resources are limited can displace medically necessary treatments. Moreover, treatments without a medical or a dental necessity, can be harmful and bear the risk of futile or excessive treatments not in patients' long-term interest. Examples in dentistry are found in the field of cosmetic interventions, prosthodontics and orthodontics, where perceptions of small 'deviations' from normality prompt wishes or recommendations for intervention. Ethically, wish-fulfilling services confront the principles of the common morality if the autonomy of a patient is compromised, beneficence is unclear, harm is foreseeable, or distributive justice is compromised. Wish-fulfilling dental treatment can be restricted by legislation if it conflicts with safe, effective and efficient care, or if it interferes with patient's real needs or undermines established professional standards. CONCLUSIONS: The general understanding of wish-fulfilling medicine including its ethical and legal themes is relevant to dentistry. CLINICAL RELEVANCE: Ethical considerations and legislation can guide a dentist to reflect critically on clinical decisions regarding wish-fulfilling dentistry.

[Wish fulfilling medicine and wish fulfilling dentistry: legal aspects]. / Wensgeneeskunde en wenstandheelkunde: juridische aspecten.

Wish fulfilling medicine (human enhancement (therapy)) concerns medical treatment without a direct medical need. In traditional medicine, a classical triad applies: 1. after investigation symptoms of illness lead to 2. a diagnosis, followed by 3. a proposal for treatment by the health care provider. In wish fulfilling medicine, the emphasis lies on patient's wishes. Wish fulfilling medicine concerns medical treatment, often at the request of the patient, and should be distinguished from shared decision-making,a form of communication seeking to meet the preferences of the patient and to actively involve the patient in his treatment. In the Netherlands, in accordance with the Healthcare Quality, Complaints and Disputes Act, health care providers have to offer good care at a good level, which is safe, effective, efficient and client-orientated, offered in a timely fashion and geared to the real needs of the client. Good care has to meet professional standards. In this way, fulfilling patients' wishes for treatment without a medical need can be restricted by law.

[Wish fulfilling medicine and wish fulfilling dentistry: -medical-ethical aspects]. / Wensgeneeskunde en wenstandheel­kunde: medisch-ethische aspecten.

Wish fulfilling medicine comprises medical procedures applied without a direct medical need. In such procedures, the medical-ethical principles can come under pressure: the autonomy of the patient, when wishes originate from social pressure; beneficence when the (underlying) aim and consequences are unclear; and 'doing no harm', when that appears to be impossible. The principle of justice, too, could come under threat when especially those with a privileged socio-economic background can take advantage of wish fulfilling medicine. Regardless of whether it concerns wish fulfilling medicine or conventional medicine, respect for human dignity and the individual integrity of the patient continue to be paramount. In care ethics and moral ethics, the qualities necessary in a proper caregiver are emphasised, such as caring, compassion, commitment, honesty and personal dedication. Wish fulfilling medicine is the subject of significant ethical debate. Important aspects arising from this debate are that the risks of harm should be limited, human dignity and integrity should be respected, people should genuinely be helped and the principle of justice should be upheld.

[Wish fulfilling medicine and wish fulfilling dentistry: what does this mean?] / Wensgeneeskunde en wens­tandheelkunde: wat wordt ermee bedoeld?

Wish fulfilling medicine refers to medical procedures applied without a direct medical need. In wish fulfilling medicine, the wish of the patient is dominant, but wish fulfilling medicine is also promoted indirectly by healthcare providers, (pharmaceutical) companies and healthcare insurers. Wish fulfilling medicine often concerns the enhancement of appearance or performance; therefore, wish fulfilling medicine is also referred to as (human) enhancement (therapy). The line between traditional and wish fulfilling medicine is vague: the border between illness and health, normal and abnormal functioning is not sharply defined and is relative to time and place. In the Netherlands, wish fulfilling medicine is not covered in the basic package provided by healthcare insurers and is paid for by the patients themselves. However, 'pay yourself' is not a decisive criterion for wish fulfilling medicine. With new biotechnological developments the domain of wish fulfilling medicine is expanding. Some dental treatments can be considered as wish fulfilling dentistry, for example in the context of cosmetic dentistry, orthodontics, or dental implantology. Although wish fulfilling medical treatments do not cure disease, they can promote health.

Evaluation of accelerated iterative x-ray CT image reconstruction using floating point graphics hardware.

Statistical reconstruction methods offer possibilities to improve image quality as compared with analytical methods, but current reconstruction times prohibit routine application in clinical and micro-CT. In particular, for cone-beam x-ray CT, the use of graphics hardware has been proposed to accelerate the forward and back-projection operations, in order to reduce reconstruction times. In the past, wide application of this texture hardware mapping approach was hampered owing to limited intrinsic accuracy. Recently, however, floating point precision has become available in the latest generation commodity graphics cards. In this paper, we utilize this feature to construct a graphics hardware accelerated version of the ordered subset convex reconstruction algorithm. The aims of this paper are (i) to study the impact of using graphics hardware acceleration for statistical reconstruction on the reconstructed image accuracy and (ii) to measure the speed increase one can obtain by using graphics hardware acceleration. We compare the unaccelerated algorithm with the graphics hardware accelerated version, and for the latter we consider two different interpolation techniques. A simulation study of a micro-CT scanner with a mathematical phantom shows that at almost preserved reconstructed image accuracy, speed-ups of a factor 40 to 222 can be achieved, compared with the unaccelerated algorithm, and depending on the phantom and detector sizes. Reconstruction from physical phantom data reconfirms the usability of the accelerated algorithm for practical cases.

Parallel statistical image reconstruction for cone-beam x-ray CT on a shared memory computation platform.

Statistical reconstruction methods offer possibilities of improving image quality as compared to analytical methods, but current reconstruction times prohibit routine clinical applications. To reduce reconstruction times we have parallelized a statistical reconstruction algorithm for cone-beam x-ray CT, the ordered subset convex algorithm (OSC), and evaluated it on a shared memory computer. Two different parallelization strategies were developed: one that employs parallelism by computing the work for all projections within a subset in parallel, and one that divides the total volume into parts and processes the work for each sub-volume in parallel. Both methods are used to reconstruct a three-dimensional mathematical phantom on two different grid densities. The reconstructed images are binary identical to the result of the serial (non-parallelized) algorithm. The speed-up factor equals approximately 30 when using 32 to 40 processors, and scales almost linearly with the number of cpus for both methods. The huge reduction in computation time allows us to apply statistical reconstruction to clinically relevant studies for the first time.

Statistical image reconstruction for transmission tomography using relaxed ordered subset algorithms.

Statistical reconstruction methods offer possibilities for improving image quality as compared to analytical methods, but current reconstruction times prohibit routine clinical applications in x-ray computed tomography (CT). To reduce reconstruction times, we have applied (under) relaxation to ordered subset algorithms. This enables us to use subsets consisting of only single projection angle, effectively increasing the number of image updates within an entire iteration. A second advantage of applying relaxation is that it can help improve convergence by removing the limit cycle behaviour of ordered subset algorithms, which normally do not converge to an optimal solution but rather a suboptimal limit cycle consisting of as many points as there are subsets. Relaxation suppresses the limit cycle behaviour by decreasing the stepsize for approaching the solution. A simulation study for a 2D mathematical phantom and three different ordered subset algorithms shows that all three algorithms benefit from relaxation: equal noise-to-resolution trade-off can be achieved using fewer iterations than the conventional algorithms, while a lower minimal normalized mean square error (NMSE) clearly indicates a better convergence. Two different schemes for setting the relaxation parameter are studied, and both schemes yield approximately the same minimal NMSE.

Evaluation of the ordered subset convex algorithm for cone-beam CT.

Statistical methods for image reconstruction such as maximum likelihood expectation maximization (ML-EM) are more robust and flexible than analytical inversion methods and allow for accurate modelling of the photon transport and noise. Statistical reconstruction is prohibitively slow when applied to clinical x-ray cone-beam CT due to the large data sets and the high number of iterations required for reconstructing high resolution images. One way to reduce the reconstruction time is to use ordered subsets of projections during the iterations, which has been successfully applied to fan-beam x-ray CT. In this paper, we quantitatively analyse the use of ordered subsets in concert with the convex algorithm for cone-beam x-ray CT reconstruction, for the case of circular acquisition orbits. We focus on the reconstructed image accuracy of a 3D head phantom. Acceleration factors larger than 300 were obtained with errors smaller than 1%, with the preservation of signal-to-noise ratio. Pushing the acceleration factor towards 600 by using an increasing number of subsets increases the reconstruction error up to 5% and significantly increases noise. The results indicate that the use of ordered subsets can be extremely useful for cone-beam x-ray CT.

One-step finite-difference time-domain algorithm to solve the Maxwell equations.

We present a one-step algorithm to solve the time-dependent Maxwell equations for systems with spatially varying permittivity and permeability. We compare the results of this algorithm with those obtained from the Yee algorithm and from unconditionally stable algorithms. We demonstrate that for a range of applications the one-step algorithm may be orders of magnitude more efficient than multiple time-step, finite-difference time-domain algorithms. We discuss both the virtues and limitations of this one-step approach.

Higher-order unconditionally stable algorithms to solve the time-dependent Maxwell equations.

For the recently introduced algorithms to solve the time-dependent Maxwell equations [J. S. Kole, M. T. Figge, and H. De Raedt, Phys. Rev. E 64, 066705 (2001)], we construct a variable grid implementation and an improved spatial discretization implementation that preserve the exceptional property of the algorithms to be unconditionally stable by construction. We find that the performance and accuracy of the corresponding algorithms are significant and illustrate their practical relevance by simulating various physical model systems.

Unconditionally stable algorithms to solve the time-dependent Maxwell equations.

Based on the Suzuki product-formula approach, we construct a family of unconditionally stable algorithms to solve the time-dependent Maxwell equations. We describe a practical implementation of these algorithms for one-, two-, and three-dimensional systems with spatially varying permittivity and permeability. The salient features of the algorithms are illustrated by computing selected eigenmodes and the full density of states of one-, two-, and three-dimensional models and by simulating the propagation of light in slabs of photonic band-gap materials.

Quantum Monte Carlo method for attractive Coulomb potentials.

Starting from an exact lower bound on the imaginary-time propagator, we present a path-integral quantum Monte Carlo method that can handle singular attractive potentials. We illustrate the basic ideas of this quantum Monte Carlo algorithm by simulating the ground state of hydrogen and helium.

Morphological image analysis of quantum motion in billiards.

Morphological image analysis is applied to the time evolution of the probability distribution of a quantum particle moving in two- and three-dimensional billiards. It is shown that the time-averaged Euler characteristic of the probability distribution provides a well defined quantity to distinguish between classically integrable and nonintegrable billiards. In three dimensions the time-averaged mean breadth of the probability distribution may also be used for this purpose.

Repair of CFTR mRNA by spliceosome-mediated RNA trans-splicing.

Most messenger RNA precursors (pre-mRNA) undergo cis-splicing in which introns are excised and the adjoining exons from a single pre-mRNA are ligated together to form mature messenger RNA. This reaction is driven by a complex known as the spliceosome. Spliceosomes can also combine sequences from two independently transcribed pre-mRNAs in a process known as trans-splicing. Spliceosome-mediated RNA trans-splicing (SMaRT) is an emerging technology in which RNA pre-therapeutic molecules (PTMs) are designed to recode a specific pre-mRNA by suppressing cis-splicing while enhancing trans-splicing between the PTM and its pre-mRNA target. This study examined the feasibility of SMaRT as a potential therapy for genetic diseases to correct mutations using cystic fibrosis (CF) as an example. We used several versions of a cystic fibrosis transmembrane conductance regulator (CFTR) mini-gene expressing mutant (deltaF508) pre-mRNA targets and tested this against a number of PTMs capable of binding to the CFTR target intron 9 and trans-splicing in the normal coding sequences for exons 10-24 (containing F508). When 293T cells were cotransfected with both constructs, they produced a trans-spliced mRNA in which normal exon 10-24 replaced mutant exon 10. To test whether SMaRT produced mature CFTR protein, proteins were immunoprecipitated from lysates of cotransfected cells and detected by Western blotting and PKA-phosphorylation. Tryptic phosphopeptide mapping confirmed the identity of CFTR. This proof-of-concept study demonstrates that exon replacement by SMaRT can repair an abnormal pre-mRNA associated with a genetic disease.

Correction of aberrant splicing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by antisense oligonucleotides.

The CFTR splicing mutation 3849 + 10 kb C --> T creates a novel donor site 10 kilobases (kb) into intron 19 of the gene and is one of the more common splicing mutations that causes cystic fibrosis (CF). It has an elevated prevalence among patients with atypically mild disease and normal sweat electrolytes and is especially prominent in Ashkenazi Jews. This class of splicing mutations, reported in several genes, involves novel splice sites activated deep within introns while leaving wild-type splice elements intact. CFTR cDNA constructs that modeled the 3849 + 10 kb C --> T mutation were expressed in 3T3 mouse fibroblasts and in CFT1 human tracheal and C127 mouse mammary epithelial cells. In all three cell types, aberrant splicing of CFTR pre-mRNA was comparable to that reported in vivo in CF patients. Treatment of the cells with 2'-O-methyl phosphorothioate oligoribonucleotides antisense toward the aberrant donor and acceptor splice sites or to the retained exon-like sequence, disfavored aberrant splicing and enhanced normal processing of CFTR pre-mRNA. This antisense-mediated correction of splicing was dose- and sequence-dependent and was accompanied by increased production of CFTR protein that was appropriately glycosylated. Antisense-mediated correction of splicing in a mutation-specific context represents a potential gene therapy modality with applicability to many inherited disorders.

Gene targeting of a CFTR allele in HT29 human epithelial cells.

HT29 cells endogenously express the cystic fibrosis transmembrane conductance regulator (CFTR) and have been used previously as a model to examine cellular regulation of CFTR expression and chloride secretory function. Homologous recombination has been used to specifically disrupt CFTR transcription in the HT29-18-C1 subclone. Experiments demonstrate successful disruption of a CFTR allele by DNA constructs, which target insertion of the neomycin phosphotransferase gene into CFTR exon 1 via homologous recombination. The mutation of one allele is a partial knockout because this cell line has multiple CFTR alleles. The mutation is confirmed by polymerase chain reaction (PCR) and genomic Southern blot analysis. A 52-68% reduction in CFTR mRNA levels is observed in the mutant cell line by both Northern and PCR analysis. However, Western blots show no decrease in total CFTR protein levels. Consistent with the lack of reduction in CFTR protein, the partial knockout mutant does not demonstrate alterations in cyclic AMP or calcium stimulation of chloride efflux or net osmolyte loss. Results suggest that posttranscriptional regulation of CFTR levels may contribute to maintenance of cellular chloride transport function.

Protein phosphorylation responses in normal and cystic fibrosis airway epithelial cell lines.

Monolayers of SV-40 immortalized human airway epithelial cell lines were stimulated with bradykinin and isoproterenol to study protein phosphorylation responses that accompany ion transport regulation in normal (BEAS) and cystic fibrosis (CF/T43) cells. Phosphorylation responses were analyzed by two-dimensional gel electrophoresis of postmicrosomal supernatant fractions of 32Pi-labeled cells. Isoproterenol increased the labeling of three phosphoproteins of M(r) 17,000, 18,000, and 37,000 that were equivalent to proteins known to undergo cAMP-dependent phosphorylation in T84 cell monolayers. Distinct proteins showed increased phosphorylation with bradykinin, including acidic proteins of M(r) 15,000 and 29,000. These resembled proteins exhibiting Ca(2+)-dependent phosphorylation T84 cells. The CF/T43 and BEAS cell protein phosphorylation responses were indistinguishable. These findings support the concept that the regulation and function of protein kinase A is normal in cystic fibrosis airway epithelia and that the abnormal cAMP-mediated regulation of chloride permeability in these cells is due to altered regulatory or effector proteins.

Characterization of the cystic fibrosis transmembrane conductance regulator in a colonocyte cell line.

An anti-peptide antibody raised to the C-terminal sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) was used to examine CFTR immunoreactivity in the T84 colonocyte cell line. Immunoblots of T84 cell lysates detected CFTR as a 170-kDa protein that appeared as a broad band or doublet in SDS/PAGE. This protein comigrated with the predominant immunoblot signal detected in human pancreas and colon. An equivalent protein was detected as a prominent substrate for protein kinase A and for protein kinase C in T84 cell immunoprecipitates with this antibody. The immunoprecipitated protein resembled the protein detected by immunoblot in that both proteins showed the same change in electrophoretic mobility after digestion by N-Glycanase. The precipitated protein was indentified as CFTR by two criteria. First, the same protein was immunoprecipitated with an antibody to a different CFTR peptide, [Lys102]CFTR-(102-116). Second, two-dimensional phosphopeptide mapping was used to compare the immunoprecipitated protein with a bacterially expressed protein known to contain most of the predicted protein kinase A phosphorylation sites in CFTR. Because the six most prominent peptides in each map were equivalent, these maps confirm that the precipitated protein is CFTR. By using these antibodies for immunofluorescence and immunoperoxidase staining, CFTR was localized to the apical region of T84 cells grown in tumors and in monolayers. Thus, T84 cells express CFTR at sufficient levels to permit identification and immunochemical studies of this protein in its endogenously occurring form.