The Lausanne Institutional Biobank: a new resource to catalyse research in personalised medicine and pharmaceutical sciences.

Breakthrough technologies which now enable the sequencing of individual genomes will irreversibly modify the way diseases are diagnosed, predicted, prevented and treated. For these technologies to reach their full potential requires, upstream, access to high-quality biomedical data and samples from large number of properly informed and consenting individuals and, downstream, the possibility to transform the emerging knowledge into a clinical utility. The Lausanne Institutional Biobank was designed as an integrated, highly versatile infrastructure to harness the power of these emerging technologies and catalyse the discovery and development of innovative therapeutics and biomarkers, and advance the field of personalised medicine. Described here are its rationale, design and governance, as well as parallel initiatives which have been launched locally to address the societal, ethical and technological issues associated with this new bio-resource. Since January 2013, inpatients admitted at Lausanne CHUV University Hospital have been systematically invited to provide a general consent for the use of their biomedical data and samples for research, to complete a standardised questionnaire, to donate a 10-ml sample of blood for future DNA extraction and to be re-contacted for future clinical trials. Over the first 18 months of operation, 14,459 patients were contacted, and 11,051 accepted to participate in the study. This initial 18-month experience illustrates that a systematic hospital-based biobank is feasible; it shows a strong engagement in research from the patient population in this University Hospital setting, and the need for a broad, integrated approach for the future of medicine to reach its full potential

Observation of Spin Flips with a Single Trapped Proton

Radio-frequency induced spin transitions of one individual proton are observed for the first time. The spin quantum jumps are detected via the continuous Stern-Gerlach effect, which is used in an experiment with a single proton stored in a cryogenic Penning trap. This is an important milestone towards a direct high-precision measurement of the magnetic moment of the proton and a new test of the matter-antimatter symmetry in the baryon sector

Resolution of Single Spin-Flips of a Single Proton

The spin magnetic moment of a single proton in a cryogenic Penning trap was coupled to the particle's axial motion with a superimposed magnetic bottle. Jumps in the oscillation frequency indicate spin-flips and were identified using a Bayesian analysis.Comment: accepted for publication by Phys. Rev. Lett., submitted 6.June.201

High participation rate among 25 721 patients with broad age range in a hospital-based research project involving whole-genome sequencing - the Lausanne Institutional Biobank.

We aimed to evaluate the interest of adult inpatients and selected outpatients in engaging in a large, real-life, hospital-based, genomic medicine research project and in receiving clinically actionable incidental findings. Within the framework of the cross-sectional Institutional Biobank of Lausanne, Switzerland, a total of 25721 patients of the CHUV University Hospital were systematically invited to grant researchers access to their biomedical data and to donate blood for future analyses, including whole-genome sequencing. Multivariable logistic regression analysis was used to identify personal factors, including age, gender, religion, ethnicity, citizenship, education level and mode of admission, associated with willingness to participate in this genomic research project and with interest in receiving clinically actionable incidental findings. The overall participation rate was 79% (20343/25721). Participation rate declined progressively with age, averaging 83%, 75%, 67% and 62% in patients aged <64 years (n = 13108), ≥64 years (n = 12613), ≥80 years (n = 4557) and ≥90 years (n = 1050), respectively. Factors associated with participation substantially differed between age strata. Patients less likely to participate included women (odds ratio 0.86, [95% confidence interval 0.79-0.95] and 0.78 [0.71-0.85] before and after age 64, respectively), non-Swiss (0.81 [0.74-0.90] and 0.58 [0.52-0.65]) and those admitted through the emergency ward (0.88 [0.79-0.98] and 0.66 [0.60-0.73]). Religion and marital status were associated with participation among patients aged <64 years. A total of 19 018 (93%) participants were willing to be re-contacted for incidental findings. A high education level was associated with higher participation rate, but not with higher willingness to receive incidental findings within the population who had agreed to participate. A large proportion of adult patients, even among the elderly, are willing to actively participate and receive incidental findings in this systematic hospital-based precision and genomic medicine research program with broad consent

Demonstration of the Double Penning Trap Technique with a Single Proton

Spin flips of a single proton were driven in a Penning trap with a homogeneous magnetic field. For the spin-state analysis the proton was transported into a second Penning trap with a superimposed magnetic bottle, and the continuous Stern-Gerlach effect was applied. This first demonstration of the double Penning trap technique with a single proton suggests that the antiproton magnetic moment measurement can potentially be improved by three orders of magnitude or more

Toll-Interacting Protein Regulates Immune Cell Infiltration and Promotes Colitis-Associated Cancer.

Expression of Toll-interacting protein (Tollip), a potent TLR modulator, decreases in patients with inflammatory bowel diseases (IBD), whereas Tollip <sup>-/-</sup> mice are susceptible to colitis. Tollip expression was shown to be reduced in sporadic adenoma . In contrast, we found variable Tollip expression in patients with colitis-associated adenomas. In Tollip <sup>-/-</sup> mice challenged to develop colitis-associated cancer (CAC), tumor formation was significantly reduced owing to decreased mucosal proliferative and apoptotic indexes. This protection was associated with blunt inflammatory responses without significant changes in microbial composition. mRNA expression of Cd62l and Ccr5 homing receptors was reduced in colons of untreated Tollip <sup>-/-</sup> mice, whereas CD62L <sup>+</sup> CD8 <sup>+</sup> T cells accumulated in the periphery. In Tollip-deficient adenomas Ctla-4 mRNA expression and tumor-infiltrating CD4 <sup>+</sup> Foxp3 <sup>+</sup> regulatory T cell (Treg) were decreased. Our data show that protection from CAC in Tollip-deficient mice is associated with defects in lymphocyte accumulation and composition in colitis-associated adenomas

Direct high-precision measurement of the magnetic moment of the proton

The spin-magnetic moment of the proton $\mu_p$ is a fundamental property of this particle. So far $\mu_p$ has only been measured indirectly, analysing the spectrum of an atomic hydrogen maser in a magnetic field. Here, we report the direct high-precision measurement of the magnetic moment of a single proton using the double Penning-trap technique. We drive proton-spin quantum jumps by a magnetic radio-frequency field in a Penning trap with a homogeneous magnetic field. The induced spin-transitions are detected in a second trap with a strong superimposed magnetic inhomogeneity. This enables the measurement of the spin-flip probability as a function of the drive frequency. In each measurement the proton's cyclotron frequency is used to determine the magnetic field of the trap. From the normalized resonance curve, we extract the particle's magnetic moment in units of the nuclear magneton $\mu_p=2.792847350(9)\mu_N$. This measurement outperforms previous Penning trap measurements in terms of precision by a factor of about 760. It improves the precision of the forty year old indirect measurement, in which significant theoretical bound state corrections were required to obtain $\mu_p$, by a factor of 3. By application of this method to the antiproton magnetic moment $\mu_{\bar{p}}$ the fractional precision of the recently reported value can be improved by a factor of at least 1000. Combined with the present result, this will provide a stringent test of matter/antimatter symmetry with baryons.Comment: published in Natur

Towards a high-precision measurement of the antiproton magnetic moment

The recent observation of single spins flips with a single proton in a Penning trap opens the way to measure the proton magnetic moment with high precision. Based on this success, which has been achieved with our apparatus at the University of Mainz, we demonstrated recently the first application of the so called double Penning-trap method with a single proton. This is a major step towards a measurement of the proton magnetic moment with ppb precision. To apply this method to a single trapped antiproton our collaboration is currently setting up a companion experiment at the antiproton decelerator of CERN. This effort is recognized as the Baryon Antibaryon Symmetry Experiment (BASE). A comparison of both magnetic moment values will provide a stringent test of CPT invariance with baryons.Comment: Submitted to LEAP 2013 conference proceeding

Investigation of acceptor levels and hole scattering mechanisms in p-gallium selenide by means of transport measurements under pressure

The effect of pressure on acceptor levels and hole scattering mechanisms in p-GaSe is investigated through Hall effect and resistivity measurements under quasi-hydrostatic conditions up to 4 GPa. The pressure dependence of the hole concentration is interpreted through a carrier statistics equation with a single (nitrogen) or double (tin) acceptor whose ionization energies decrease under pressure due to the dielectric constant increase. The pressure effect on the hole mobility is also accounted for by considering the pressure dependencies of both the phonon frequencies and the hole-phonon coupling constants involved in the scattering rates.Comment: 13 pages, Latex, 4 ps figures. to appear in High Pressure Research 69 (1997

An Innovative Approach to Determine Coastal Scenic Beauty and Sensitivity in a Scenario of Increasing Human Pressure and Natural Impacts due to Climate Change

Coasts worldwide face a great variety of environmental impacts, as well as increased anthropogenic pressures due to urbanization and rapid population growth. Human activities menace ecosystem services and the economy of coastal countries, often based on "Sun, Sea and Sand" (3S) tourism. The five parameters of greatest importance (the "Big Five") for beach visitors are safety, facilities, water quality, no litter and scenery, and the characterization of the latter was recently carried out by means of a checklist of 26 natural and human parameters, parameter weighting matrices and fuzzy logic, according to the "Coastal Scenic Evaluation System" (CSES) methodology. In order to propose sound coastal management strategies, the main aim of this paper is to propose a method to determine the scenic sensitivity of (i) natural parameters to coastal natural processes in a Climate Change context and (ii) human parameters to visitors' pressure in a scenario of increasing tourism and coastal developments. Regarding natural parameters, the sensitivity of "Beach face" and "Dunes" parameters is determined according to an Erodibility Index with a Correction Factor, taking into account wave forcing characteristics, tidal range and trends at a local scale of Sea Level Rise and Storm Surge. This establishes a Sensitivity Index to natural processes. A site's scenic sensitivity to human pressure/activities was determined by considering the sensitivity of several human parameters of the CSES method according to beach typology and access difficulty together with the Protection Area Management Category to which a site belongs. A Human Impact Index is obtained, which is afterwards corrected by taking into account local trends of tourism pressure, establishing a Sensitivity Index to human pressure. Finally, a total Sensitivity Index considering both natural processes and human pressure is obtained, and sites divided into three sensitive groups. The results can be useful to limit and prevent environmental degradation linked to natural processes and tourism development, and also to suggest measures to improve the scenic value of investigated sites and their sustainable usage. The method was tested for 29 sites of great scenic quality along the Mediterranean coast of Andalusia, Spain