Occam's razor in minimally invasive pituitary surgery: tailoring the endoscopic endonasal uninostril trans-sphenoidal approach to sella turcica.

BACKGROUND: Since the introduction of the endoscopic endonasal approaches in the field of skull base surgery during the last two decades, several variants of the sella turcica endoscopic surgery have been described. The aim of this study is to provide a stepwise description of one of these variants in a minimally invasive/maximally efficient perspective. METHOD: For the majority of our sella turcica pathologies, we have progressively adopted a uninostril endoscopic approach that is very conservative towards the nasal mucosa with a very limited mucosal incision, resection of the vomer and allowing an almost ad integrum sellar floor reconstruction, without compromising the efficacy and completeness of both surgical oncologic and endocrine targets. CONCLUSION: The uninostril trans-sphenoidal endoscopic endonasal approach to sella turcica is tailored to ally maximal efficiency and minimal invasiveness.

The InterActive Choice Aid: A new approach to supporting online consumer decision making

Interactive Choice Aid (ICA) is a decision aid, introduced in this paper, that systematically assists consumers with online purchase decisions. ICA integrates aspects from prescriptive decision theory, insights from descriptive decision research, and practical considerations; thereby combining pre-existing best practices with novel features. Instead of imposing an objectively ideal but unnatural decision procedure on the user, ICA assists the natural process of human decision-making by providing explicit support for the execution of the user's decision strategies. The application contains an innovative feature for in-depth comparisons of alternatives through which users' importance ratings are elicited interactively and in a playful way. The usability and general acceptance of the choice aid was studied; results show that ICA is a promising contribution and provides insights that may further improve its usability.

Anorexie mentale et boutimie: I'expérience vaudoise d'une prise en charge interdisciplinaire [Anorexia and bulimia: the canton of Vaud's experience of an interdisciplinary approach].

As psychiatric disorders attacking the body, anorexia and bulimia may have severe psychological, physical and social consequences, often requiring a long-standing interdisciplinary, coordinated and individualized approach. Recently the canton of Vaud has initiated and developed an interinstitutional structure--between the University Hospital (CHUV) and the hospitals of the Northern region of the canton (eHnv)--for the care of patients suffering from eating disorders. This structure, allowing the above mentioned approach for the treatment of eating disorders, consists of an outpatient facility located in the CHUV and an inpatient unit in the hospital of Saint Loup of the eHnv. Within this structure, the general practitioner plays a crucial role in the prevention of the chronification of these disorders by means of their early detection and management.

A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR.

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray.

Immersion communautaire à Lausanne : une autre façon d'enseigner la santé publique [Community immersion in Lausanne: a different approach to teaching public health?].

Teaching community medicine represents a significant challenge for medical schools, which tend to struggle to promote interest in the issue among students. In 2009, the Lausanne medical school introduced a "community immersion" module specifically designed to address the issue. The new module requires students working in small groups under the supervision of a tutor to investigate a health question of their choice. The investigation involves conducting interviews with stakeholders (health professionals, patients, politicians, etc.), carrying out a survey, and presenting the results of the investigation in a "congress". An external evaluation showed that the objectives of the initiative had been largely achieved, with an increase of interest in community medicine for over 50% of students (based on a total cohort of 150 students) and a high level of satisfaction for over 90% of students and tutors. This paper presents the results of the initiative and its use for promoting community-oriented medicine.

Targeting Cancer Stem-like Cells as an Approach to Defeating Cellular Heterogeneity in Ewing Sarcoma.

Plasticity in cancer stem-like cells (CSC) may provide a key basis for cancer heterogeneity and therapeutic response. In this study, we assessed the effect of combining a drug that abrogates CSC properties with standard-of-care therapy in a Ewing sarcoma family tumor (ESFT). Emergence of CSC in this setting has been shown to arise from a defect in TARBP2-dependent microRNA maturation, which can be corrected by exposure to the fluoroquinolone enoxacin. In the present work, primary ESFT from four patients containing CD133(+) CSC subpopulations ranging from 3% to 17% of total tumor cells were subjected to treatment with enoxacin, doxorubicin, or both drugs. Primary ESFT CSC and bulk tumor cells displayed divergent responses to standard-of-care chemotherapy and enoxacin. Doxorubicin, which targets the tumor bulk, displayed toxicity toward primary adherent ESFT cells in culture but not to CSC-enriched ESFT spheres. Conversely, enoxacin, which enhances miRNA maturation by stimulating TARBP2 function, induced apoptosis but only in ESFT spheres. In combination, the two drugs markedly depleted CSCs and strongly reduced primary ESFTs in xenograft assays. Our results identify a potentially attractive therapeutic strategy for ESFT that combines mechanism-based targeting of CSC using a low-toxicity antibiotic with a standard-of-care cytotoxic drug, offering immediate applications for clinical evaluation.

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

AIMS: A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. METHODS: A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.

A design science approach to support the assessment of disruptive technology : the Swiss mobile payment case

Abstract In this thesis we present the design of a systematic integrated computer-based approach for detecting potential disruptions from an industry perspective. Following the design science paradigm, we iteratively develop several multi-actor multi-criteria artifacts dedicated to environment scanning. The contributions of this thesis are both theoretical and practical. We demonstrate the successful use of multi-criteria decision-making methods for technology foresight. Furthermore, we illustrate the design of our artifacts using build and-evaluate loops supported with a field study of the Swiss mobile payment industry. To increase the relevance of this study, we systematically interview key Swiss experts for each design iteration. As a result, our research provides a realistic picture of the current situation in the Swiss mobile payment market and reveals previously undiscovered weak signals for future trends. Finally, we suggest a generic design process for environment scanning.

A novel approach to reducing number of sensing units for wearable gait analysis systems.

Gait analysis methods to estimate spatiotemporal measures, based on two, three or four gyroscopes attached on lower limbs have been discussed in the literature. The most common approach to reduce the number of sensing units is to simplify the underlying biomechanical gait model. In this study, we propose a novel method based on prediction of movements of thighs from movements of shanks. Datasets from three previous studies were used. Data from the first study (ten healthy subjects and ten with Parkinson's disease) were used to develop and calibrate a system with only two gyroscopes attached on shanks. Data from two other studies (36 subjects with hip replacement, seven subjects with coxarthrosis, and eight control subjects) were used for comparison with the other methods and for assessment of error compared to a motion capture system. Results show that the error of estimation of stride length compared to motion capture with the system with four gyroscopes and our new method based on two gyroscopes was close ( -0.8 ±6.6 versus 3.8 ±6.6 cm). An alternative with three sensing units did not show better results (error: -0.2 ±8.4 cm). Finally, a fourth that also used two units but with a simpler gait model had the highest bias compared to the reference (error: -25.6 ±7.6 cm). We concluded that it is feasible to estimate movements of thighs from movements of shanks to reduce number of needed sensing units from 4 to 2 in context of ambulatory gait analysis.

Missed appointments in an outpatient clinic for adolescents, an approach to predict the risk of missing.

PURPOSE: To predict the risk of an adolescent patient to miss an appointment, based on the previous appointments and on the characteristics of the patient and the appointment. METHODS: Two thousand one hundred ninety-three (1873 females) patients aged 12 to 20 years having scheduled at least four appointments were included. We assessed the rate of missed nonexcused appointments of each patient. Second, a Markovian multilevel model was used to predict the risk of defaulting. RESULTS: Forty-five percent of the patients have not missed even once, and 14% of females and 17% of males have missed &gt;25% of their appointments. Females show two types of behaviors (an abstract concept that groups individuals based on a combination of their appointment-keeping and their recorded type of healthcare need) depending on the diagnosis. Somatic, gynecology, violence, and counseling diagnoses are mostly grouped together. In this group, having already missed and having an appointment with a paramedical provider increases the risk of missing. In the second group (eating disorders and psychiatric diagnoses) having already missed and a longer delay between appointments influence the risk of missing, although the risk is lower for this latter group. Males only show one type of behavior regarding missed appointments. Having missed a previous appointment, being older, having cancelled the next to last appointment and the type of diagnosis explain the risk of missing. CONCLUSIONS: Patients who have already defaulted have a higher risk of defaulting again. Means of control regarding missed appointments should consequently focus on defaulters, to decrease the associated workload. Reminders could be a solution for the follow-up appointments scheduled with a long delay.

Use of a Mendelian randomization approach to assess the causal relation of gamma-Glutamyltransferase with blood pressure and serum insulin levels.

Elevated levels of γ-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a cross-sectional analysis (2003-2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the γ-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P's < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: β -5.68, 95% confidence interval (CI): -11.51, 0.16 (P = 0.06); diastolic: β = -2.24, 95% CI: -5.98, 1.49 (P = 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (β = 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (β = 0.19, 95% CI: 0.01, 0.37; P = 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP.

A novel approach to characterize clonality and differentiation of human melanoma-specific T cell responses: spontaneous priming and efficient boosting by vaccination.

Despite major progress in T lymphocyte analysis in melanoma patients, TCR repertoire selection and kinetics in response to tumor Ags remain largely unexplored. In this study, using a novel ex vivo molecular-based approach at the single-cell level, we identified a single, naturally primed T cell clone that dominated the human CD8(+) T cell response to the Melan-A/MART-1 Ag. The dominant clone expressed a high-avidity TCR to cognate tumor Ag, efficiently killed tumor cells, and prevailed in the differentiated effector-memory T lymphocyte compartment. TCR sequencing also revealed that this particular clone arose at least 1 year before vaccination, displayed long-term persistence, and efficient homing to metastases. Remarkably, during concomitant vaccination over 3.5 years, the frequency of the pre-existing clone progressively increased, reaching up to 2.5% of the circulating CD8 pool while its effector functions were enhanced. In parallel, the disease stabilized, but subsequently progressed with loss of Melan-A expression by melanoma cells. Collectively, combined ex vivo analysis of T cell differentiation and clonality revealed for the first time a strong expansion of a tumor Ag-specific human T cell clone, comparable to protective virus-specific T cells. The observed successful boosting by peptide vaccination support further development of immunotherapy by including strategies to overcome immune escape.

Liberties and constraints of the normative approach to evaluation and decision in forensic science: a discussion towards overcoming some common misconceptions

At a time when disciplined inference and decision making under uncertainty represent common aims to participants in legal proceedings, the scientific community is remarkably heterogenous in its attitudes as to how these goals ought to be achieved. Probability and decision theory exert a considerable influence, and we think by all reason rightly do so, but they go against a mainstream of thinking that does not embrace-or is not aware of-the 'normative' character of this body of theory. It is normative, in the sense understood in this article, in that it prescribes particular properties, typically (logical) coherence, to which reasoning and decision making ought to conform. Disregarding these properties can result in diverging views which are occasionally used as an argument against the theory, or as a pretext for not following it. Typical examples are objections according to which people, both in everyday life but also individuals involved at various levels in the judicial process, find the theory difficult to understand and to apply. A further objection is that the theory does not reflect how people actually behave. This article aims to point out in what sense these examples misinterpret the analytical framework in its normative perspective. Through examples borrowed mostly from forensic science contexts, it is argued that so-called intuitive scientific attitudes are particularly liable to such misconceptions. These attitudes are contrasted with a statement of the actual liberties and constraints of probability and decision theory and the view according to which this theory is normative.