A coupled model for the dynamics of gas exchanges in the human lung with Haldane and Bohr's effects.

We propose an integrated dynamical model for oxygen and carbon dioxide transfer from the lung into the blood, coupled with a lumped mechanical model for the ventilation process, for healthy patients as well as in pathological cases. In particular, we take into account the nonlinear interaction between oxygen and carbon dioxide in the blood volume, referred to as the Bohr and Haldane effects. We also propose a definition of the physiological dead space volume (the lung volume that does not contribute to gas exchange) which depends on the pathological state and the breathing scenario. This coupled ventilation-gas diffusion model is driven by the sole action of the respiratory muscles. We analyse its sensitivity with respect to characteristic parameters: the resistance of the bronchial tree, the elastance of the lung tissue and the oxygen and carbon dioxide diffusion coefficients of the alveolo-capillary membrane. Idealized pathological situations are also numerically investigated. We obtain realistic qualitative tendencies, which represent a first step towards classification of the pathological behaviours with respect to the considered input parameters.

[Experience of an interprofessional family practice in a medical residency pathways]. / Expérience d'un médecin assistant dans un cabinet de médecine de famille interprofessionnel.

This article is based on an experience during family medicine residency in a family medicine practice participating in the MOCCA project (Coordination model in family medicine practices). This new model of care integrates a family medicine nurse (FMN) into the team of each practice. Three clinical vignettes and an interview with the people involved provide a better understanding of the new role that the FMN can play in medical practices. In these situations, we note an increase in the possibilities of acting in prevention and health promotion as well as a reinforcement in the continuity of care. An experience of this type during medical residency is not common in Switzerland, because Switzerland is in the early stages of development of these new models of care in international comparison.

Cet article est né d'une expérience d'un médecin assistant au sein d'un cabinet de médecine de famille participant au projet MOCCA (modèle de coordination dans les cabinets de médecine de famille). Ce nouveau modèle de soins intègre dans l'équipe de chaque cabinet un-e infirmier-ère en médecine de famille (IMF). Trois vignettes cliniques et une interview des personnes concernées permettent de mieux comprendre le rôle nouveau que peut prendre l'IMF dans les cabinets médicaux. Dans ces situations, on constate l'augmentation des possibilités d'agir dans les domaines de la prévention et de la promotion de la santé ainsi qu'un renforcement dans la continuité des soins. Une expérience de ce type lors du parcours de médecin assistant-e n'est pas fréquente car la Suisse est au stade initial du développement de ces nouveaux modèles de soins en comparaison internationale.

Optimizing schools' start time and bus routes.

Maintaining a fleet of buses to transport students to school is a major expense for school districts. To reduce costs by reusing buses between schools, many districts spread start times across the morning. However, assigning each school a time involves estimating the impact on transportation costs and reconciling additional competing objectives. Facing this intricate optimization problem, school districts must resort to ad hoc approaches, which can be expensive, inequitable, and even detrimental to student health. For example, there is medical evidence that early high school starts are impacting the development of an entire generation of students and constitute a major public health crisis. We present an optimization model for the school time selection problem (STSP), which relies on a school bus routing algorithm that we call biobjective routing decomposition (BiRD). BiRD leverages a natural decomposition of the routing problem, computing and combining subproblem solutions via mixed integer optimization. It significantly outperforms state-of-the-art routing methods, and its implementation in Boston has led to $5 million in yearly savings, maintaining service quality for students despite a 50-bus fleet reduction. Using BiRD, we construct a tractable proxy to transportation costs, allowing the formulation of the STSP as a multiobjective generalized quadratic assignment problem. Local search methods provide high-quality solutions, allowing school districts to explore tradeoffs between competing priorities and choose times that best fulfill community needs. In December 2017, the development of this method led the Boston School Committee to unanimously approve the first school start time reform in 30 years.

Water Flow Variability Affects Adsorption and Oxidation of Ciprofloxacin onto Hematite.

The mobility of pharmaceuticals in environmental systems is under great scrutiny in the scientific literature and in the press. Still, very few reports have focused on redox-driven transformations when these compounds are bound to mineral surfaces, and how their transport is affected under flow-through conditions. In this study, we examined the adsorption and electron transfer reactions of ciprofloxacin (CIP) in a dynamic column containing nanosized hematite (α-Fe2O3). CIP binding and the subsequent redox transformation were strongly dependent on inflow pH and residence time. These reactions could be predicted using transport models that account for adsorption and transformation kinetics. Our results show that flow interruption over a 16 h period triggers oxidation of hematite-bound CIP into byproducts. These reactions are likely facilitated by inner-sphere iron-CIP complexes formed via the sluggish conversion from outer-sphere complexes during interrupted flow. When intermittent flow/no-flow conditions were applied sequentially, a second byproduct was detected in the column effluent. This work sheds light on a much overseen aspect of redox transformations of antibiotics under flow-through conditions. It has important implications in adequately predicting transport, and in developing risk assessments of these emerging compounds in the environment.

Large optics metrology for high-power lasers.

The Laser MégaJoule (LMJ) is a high-power laser dedicated to laser-plasma experiments. At the beginning of the project in the mid-1990s, an optical metrology laboratory was created at CEA to help accomplish all the steps in the construction of this laser. This paper proposes an overview of the capabilities of this metrology laboratory in four main fields: surface imperfections, photometry, laser damage measurement, and wavefront measurement. The specificities for high-power laser optics in each domain are highlighted as well as the specific features that make our instruments unique.

Swiss students and young physicians want a flexible goal-oriented GP training curriculum.

BACKGROUND: A growing shortage of general practitioners (GPs), in Switzerland and around the world, has forced countries to find new ways to attract young physicians to the specialty. In 2017, Switzerland began to fund hundreds of new study places for medical students. This wave of young physicians will soon finish University and be ready for postgraduate training. We hypothesized that an attractive postgraduate training program would encourage interested young physicians to pursue a GP career. METHODS: This is a cross-sectional survey of young physicians from the Swiss Young General Practitioners Association (JHaS), members of Cursus Romand de médecine de famille (CRMF), and all current medical students (5th or 6th years) (n = 554) in Switzerland, excluding students indicating definitely not to become GPs. We asked all if they were likely to become a GP (Likert: 1-10), and then asked them to score general features of a GP training curriculum, and likely effects of the curriculum on their career choice (Likert scale). They then rated our model curriculum (GO-GP) for attractiveness and effect (Likert Scales, open questions). RESULTS: Most participants thought they would become GPs (Likert: 8 of 10). Over 90% identified the same features as an important part of a curriculum ("yes" or "likely yes"): Our respondents thought the GO-GP curriculum was attractive (7.3 of 10). It was most attractive to those highly motivated to become GPs. After reviewing the curriculum, most respondents (58%) felt GO-GP would make them more likely to become a GP. Almost 80% of respondents thought an attractive postgraduate training program like GO-GP could motivate more young physicians to become GPs. CONCLUSIONS: Overall, medical students and young physicians found similar features attractive in the general and GO-GP curriculum, regardless of region or gender, and thought an attractive curriculum would attract more young doctors to the GP specialty. Key points An attractive postgraduate training program in general practice can attract more young physicians to become GPs. In this study cross-sectional survey including medical students (n = 242) and young physicians (n = 312) we presented general features for a curriculum and a model curriculum for general practice training, for evaluation of attractiveness to our study population. General practice training curriculum provides flexibility in choice of rotations, access to short rotations in a wide variety of medical specialties, training in specialty practices as well, mentoring and career guidance by GPs and guidance in choosing courses/certificate programs necessary for general practice. These findings help building attractive postgraduate training programs in general practice and fight GP shortage.

Oxolinic Acid Binding at Goethite and Akaganéite Surfaces: Experimental Study and Modeling.

Oxolinic acid (OA) is a widely used quinolone antibiotic in aquaculture. In this study, its interactions with synthetic goethite (α-FeOOH) and akaganéite (ß-FeOOH) particle surfaces were monitored to understand the potential fate of OA in marine sediments where these phases occur. Batch sorption experiments, liquid chromatography (LC) analyses of supernatants, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and multisite complexation (MUSIC) modeling were used to monitor OA binding at these particle surfaces. Both LC and ATR-FTIR showed that adsorption did not degrade OA, and that OA adsorption was largely unaffected by NaCl concentrations (10-1000 mM). This was explained further by ATR-FTIR suggesting the formation of metal-bonded complexes at circumneutral to low pHc = -log [H(+)] and with a strongly hydrogen-bonded complex at high pHc. The stronger OA binding to akaganéite can be explained both by the higher isoelectric point/point-of-zero charge (9.6-10) of this mineral than of goethite (9.1-9.4), and an additional OA surface complexation mechanism at the (010) plane. Geminal sites (≡Fe(OH2)2(+)) at this plane could be especially reactive for metal-bonded complexes, as they facilitate a mononuclear six-membered chelate complex via the displacement of two hydroxo/aquo groups at the equatorial plane of a single Fe octahedron. Collectively, these findings revealed that Fe-oxyhydroxides may strongly contribute to the fate and transport of OA-type antibacterial agents in marine sediments and waters.

Kinetics and Mechanisms of Ciprofloxacin Oxidation on Hematite Surfaces.

Adsorption of antibiotics at mineral surfaces has been extensively studied over the past 20 years, yet much remains to be learned on their interfacial properties and transformation mechanisms. In this study, interactions of Ciprofloxacin (CIP), a fluoroquinolone antibiotic with two sets of synthetic nanosized hematite particles, with relatively smooth (H10, 10-20 nm in diameter) and roughened (H80, 80-90 nm in diameter) surfaces, were studied by means of liquid chromatography (LC), mass spectrometry (MS), and spectroscopy (vibration and X-ray photoelectron). Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy provides evidence for inner-sphere bidentate complex formation of CIP at hematite surfaces in 0.01 M NaCl, irrespective of pH and particle size. ATR-FTIR spectroscopy also revealed that the sorbed mother CIP molecule decayed to other surface species over a period of at least 65 h. This was supported by the detection of three daughter products in the aqueous phase by LC/MS. The appearance of NH3(+) groups during the course of these experiments, revealed by cryogenic XPS, provides further evidence that CIP oxidation proceeds through an opening of piperazine ring via N-dealkylation. Additional in vacuo FTIR experiments under temperature-programmed desorption also showed that oxidation of sorbed byproducts were effectively degraded beyond 450 °C, a result denoting considerably strong (inter)molecular bonds of both mother and daughter products. This work also showed that rougher, possibly multidomainic particles (H80) generated slower rates of CIP decomposition but occurring through more complex schemes than at smoother particle surfaces (H10). This work thus uncovered key aspects of the binding of an important antibiotic at iron oxide surfaces, and therefore provided additional constraints to our growing understanding of the fate of emerging contaminants in the environment.

O6-Methylguanine-methyltransferase (MGMT) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions.

Glioblastoma (GBM) is the most malignant type of primary brain tumor with a very poor prognosis. The actual standard protocol of treatment for GBM patients consists of radiotherapy and concomitant temozolomide (TMZ). However, the therapeutic efficacy of this treatment is limited due to tumor recurrence and TMZ resistance. Recently isolated, glioma stem-like cells (GSCs) are thought to represent the population of tumorigenic cells responsible for GBM resistance and recurrence following surgery and chemotherapy. In addition, MGMT (O6-methylguanine-methyltransferase) methylation is considered as one of the principal mechanisms contributing to TMZ sensitivity of GBM. In this study we have isolated GSCs from 10 adult GBM patients and investigated the relationship between MGMT methylation status and Temozolomide (TMZ) sensitivity of these lines grown either in stem-like or differentiation promoting conditions. Sensitivity to TMZ was significantly associated with MGMT methylation status in cells committed to differentiation but not in stem-like cells. In addition, patients harboring highly methylated MGMT promoters had a longer overall survival. These results reveal the importance of the differentiation process when considering the predictive value of MGMT status in GSCs for clinical response to TMZ.

Automated segmentation of the prostate in 3D MR images using a probabilistic atlas and a spatially constrained deformable model.

PURPOSE: The authors present a fully automatic algorithm for the segmentation of the prostate in three-dimensional magnetic resonance (MR) images. METHODS: The approach requires the use of an anatomical atlas which is built by computing transformation fields mapping a set of manually segmented images to a common reference. These transformation fields are then applied to the manually segmented structures of the training set in order to get a probabilistic map on the atlas. The segmentation is then realized through a two stage procedure. In the first stage, the processed image is registered to the probabilistic atlas. Subsequently, a probabilistic segmentation is obtained by mapping the probabilistic map of the atlas to the patient's anatomy. In the second stage, a deformable surface evolves toward the prostate boundaries by merging information coming from the probabilistic segmentation, an image feature model and a statistical shape model. During the evolution of the surface, the probabilistic segmentation allows the introduction of a spatial constraint that prevents the deformable surface from leaking in an unlikely configuration. RESULTS: The proposed method is evaluated on 36 exams that were manually segmented by a single expert. A median Dice similarity coefficient of 0.86 and an average surface error of 2.41 mm are achieved. CONCLUSIONS: By merging prior knowledge, the presented method achieves a robust and completely automatic segmentation of the prostate in MR images. Results show that the use of a spatial constraint is useful to increase the robustness of the deformable model comparatively to a deformable surface that is only driven by an image appearance model.

An Online Influenza Surveillance System for Primary Care Workers in Switzerland: Observational Prospective Pilot Study.

BACKGROUND: A better understanding of the influenza epidemiology among primary care workers could guide future recommendations to prevent transmission in primary care practices. Therefore, we designed a pilot study to assess the feasibility of using a work-based online influenza surveillance system among primary care workers. Such an approach is of particular relevance in the context of the coronavirus disease (COVID-19) pandemic, as its findings could apply to other infectious diseases with similar mechanisms of transmission. OBJECTIVE: This study aims to determine the feasibility of using a work-based online influenza surveillance system for primary care workers in Switzerland. METHODS: Physicians and staff of one walk-in clinic and two selected primary care practices were enrolled in this observational prospective pilot study during the 2017-2018 influenza season. They were invited to record symptoms of influenza-like illness in a weekly online survey sent by email and to self-collect a nasopharyngeal swab in case any symptoms were recorded. Samples were tested by real-time polymerase chain reaction for influenza A, influenza B, and a panel of respiratory pathogens. RESULTS: Among 67 eligible staff members, 58% (n=39) consented to the study and 53% (n=36) provided data. From the time all participants were included, the weekly survey response rate stayed close to 100% until the end of the study. Of 79 symptomatic episodes (mean 2.2 episodes per participant), 10 episodes in 7 participants fitted the definition of an influenza-like illness case (attack rate: 7/36, 19%). One swab tested positive for influenza A H1N1 (attack rate: 3%, 95% CI 0%-18%). Swabbing was considered relatively easy. CONCLUSIONS: A work-based online influenza surveillance system is feasible for use among primary care workers. This promising methodology could be broadly used in future studies to improve the understanding of influenza epidemiology and other diseases such as COVID-19. This could prove to be highly useful in primary care settings and guide future recommendations to prevent transmission. A larger study will also help to assess asymptomatic infections.

Wer strebt am Ende des Medizinstudiums eine Hausärztekarriere an? Umfrage unter Schweizer Studierenden.

How Many Advanced Medical Students Aim for a Career as a GP? Survey among Swiss Students Abstract. According to an earlier prognosis for 2025, Switzerland will lack 5000 general practitioners (GP), since only 10-20 % of medical students wanted to choose this profession at the time of the survey. The aim of our investigation among advanced medical students was to record their career intentions anew. Beside the probability of becoming a GP, we looked at the time point of this decision and at factors around family medicine (doctor-patient relation, career possibilities, etc.) influencing this decision. The results showed that measures to promote family medicine have been successful: 60 % of interrogated students are possible GPs (20 % decided, 40 % interested), 15 % are undecided, 25 % have decided not to become a GP. The favorable factors to become a GP were: autonomy, doctor-patient relationship, possibility of part-time work, work content. Less favorable were: income, reputation, political situation. These are the points where action is required to promote careers in family medicine with attractive training and practice conditions.

Targeted RNA-sequencing assays: a step forward compared to FISH and IHC techniques?

INTRODUCTION: ALK and ROS1 rearrangements are molecular targets of several tyrosine kinase inhibitors. RNA-sequencing approaches are regarded as the new standard for fusion gene detection, representing an alternative to standard immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques. PATIENTS AND METHODS: We aimed to compare two recent amplicon-based RNA-sequencing techniques: FusionPlex® Alk Ret Ros1 v2 Kit (Archer® ) with FHS-003Z-12-Human Lung Cancer Panel (Qiagen® ) and assessed the accuracy of the data for therapy management. Thirty-seven formalin-fixed paraffin-embedded non-small cell carcinoma (NSCC) lesions initially explored by IHC and FISH were selected for RNA-sequencing analysis. RESULTS: Qiagen® and Archer® kits produced similar results and correctly identified 85.1% (23/27) and 81.5% (22/27) of IHC/FISH ALK- and ROS1-positive samples, respectively, and 100% (6/6) of the negative samples. With regard to the ambiguous IHC-positive/FISH-negative cases, RNA-sequencing confirmed 75% (3/4) of the FISH conclusion. Although not statistically significant, patients with common EML4-ALK variants presented shorter overall survival and progression-free survival compared with patients harboring rare variants. CONCLUSION: Our findings assessed the implementation of RNA-sequencing approaches to explore ALK and ROS1 rearrangements from formalin-fixed paraffin-embedded samples. We highlighted the similarities between Qiagen® and Archer® kits in terms of handling time, cost, and outcomes. We confirmed the feasibility of molecular testing in routine organization and its possible use not only as an alternative for standard IHC and FISH techniques, but as a supplementary technique helping to classify discrepant cases.

[How do we begin a medical interview? Reflections from videotapes]. / Comment commencer l'entretien médical? Réflexions sur la phase sociale à partir d'enregistrements vidéo.

The medical interview consists of several steps, each consisting of specific tasks and objectives for the doctor. The initial step of the medical consultation, the social phase, is the cornerstone in the construction of a doctor-patient relationship of trust and quality. If, in a structural point of view, the literature has responded in a clear and consistent way, questions remain openned in a procedural point of view. How successful is the physician to establish the first contact? How does he proceed to welcome his patient? We looked out ways to address these issues by the work of revising the video recordings of general medical consultations, which are regularly practiced at the Medical outpatient clinic of the University of Lausanne.

A Post-Processing Method for Three-Dimensional Electrical Impedance Tomography.

Electrical impedance tomography is a modern biomedical imaging method. Its goal is to image the electrical properties of human tissues. This approach is safe for the patient's health, is non-invasive and has no known hazards. However, the approach suffers from low accuracy. Linear inverse solvers are commonly used in medical applications, as they are strongly robust to noise. However, linear methods can give only an approximation of the solution that corresponds to a linear perturbation from an initial estimate. This paper proposes a novel reconstruction process. After applying a linear solver, the conductivity distribution is post-processed with a nonlinear algorithm, with the aim of reproducing the abrupt change in conductivity at the boundaries between tissues or organs. The results are used to compare the proposed method with three other widely used methods. The proposed method offers higher quality images and a higher robustness to noise, and significantly reduces the error associated with image reconstruction.