Orbit and trajectory measurement with low intensity lead ion beams in the SPS

The orbit measurement system of the CERN SPS was designed to measure the position of dense proton beams with an intensity of up to 0.28 A. The lower design limit for the lead ion beam intensity has been fixed at 35mA. This requires a substantial extension of the dynamic range. We describe the properties of the system and its modifications together with the results obtained for sulphur ion beams in the past and lead ions more recently

Intensity and bunch length measurement for lepton beam in the injection lines of the SPS and LEP

We describe a system which is used operationally to measure the absolute intensity of single lepton bunches in a beam transfer line. It is based on the detailed knowledge of every single item of a complex measuring chain that comprises a beam coupler on one end and an acquisition system on the other end. This knowledge can be acquired by a well tested theoretical model and careful measurement of the transfer function of each processing module. A precision better than 3 % can be obtained and no external calibration is required. A value for the bunch length can be deduced from a spectral intensity measurement at two well chosen frequencies

Steroid profiling by UHPLC-MS/MS in dried blood spots collected from healthy women with and without testosterone gel administration.

The quantification of a large panel of endogenous steroids in serum by LC-MS/MS represents a powerful clinical tool for the screening or diagnosis of diverse endocrine disorders. This approach has also demonstrated excellent sensitivity for the detection of testosterone misuse in the anti-doping field, especially in female athlete population. In both situations, the use of dried blood spots (DBS) could provide a viable alternative to invasive venous blood collection. Here, the evaluation of DBS sampling for the quantification of a panel of endogenous steroids using UHPLC-MS/MS is described. The UHPLC-MS/MS method was validated for quantitative analysis of eleven free and eight conjugated steroids and was then used for the analysis of DBS samples collected in 14 healthy women during a normal menstrual cycle (control phase) followed by a 28-days testosterone gel treatment (treatment phase). Results were compared with those obtained from serum matrix. Satisfactory performance was obtained for all compounds in terms of selectivity, linearity, accuracy, precision, combined uncertainty, stability as well as extraction recovery and matrix effects. In control phase, high correlation was observed between DBS and serum concentrations for most compounds. In treatment phase, higher testosterone concentrations were observed in capillary than in venous DBS, suggesting a possible interference resulting from testosterone contamination on finger(s) used for gel application. Steroid profiling in capillary DBS represents a simple and efficient strategy for monitoring endogenous steroid concentrations and their fluctuation in clinical context of steroid-related disorders, or for the detection of testosterone abuse in anti-doping

Straightforward quantification of endogenous steroids with liquid chromatography-tandem mass spectrometry: Comparing calibration approaches.

Different calibration strategies are used in liquid chromatography hyphenated to mass spectrometry (LC-MS) bioanalysis. Currently, the surrogate matrix and surrogate analyte represent the most widely used approaches to compensate for the lack of analyte-free matrices in endogenous compounds quantification. In this context, there is a growing interest in rationalizing and simplifying quantitative analysis using a one-point concentration level of stable isotope-labeled (SIL) standards as surrogate calibrants. Accordingly, an internal calibration (IC) can be applied when the instrument response is translated into analyte concentration via the analyte-to-SIL ratio performed directly in the study sample. Since SILs are generally used as internal standards to normalize variability between authentic study sample matrix and surrogate matrix used for the calibration, IC can be calculated even if the calibration protocol was achieved for an external calibration (EC). In this study, a complete dataset of a published and fully validated method to quantify an extended steroid profile in serum was recomputed by adapting the role of SIL internal standards as surrogate calibrants. Using the validation samples, the quantitative performances for IC were comparable with the original method, showing acceptable trueness (79%-115%) and precision (0.8%-11.8%) for the 21 detected steroids. The IC methodology was then applied to human serum samples (n = 51) from healthy women and women diagnosed with mild hyperandrogenism, showing high agreement (R <sup>2</sup> > 0.98) with the concentrations obtained using the conventional quantification based on EC. For IC, Passing-Bablok regression showed proportional biases between -15.0% and 11.3% for all quantified steroids, with an average difference of -5.8% compared to EC. These results highlight the reliability and the advantages of implementing IC in clinical laboratories routine to simplify quantification in LC-MS bioanalysis, especially when a large panel of analytes is monitored

A new multimodal paradigm for biomarkers longitudinal monitoring: a clinical application to women steroid profiles in urine and blood.

Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeling strategy to a multivariate score integrating several biomarkers (compound concentration and/or ratio). This multimodal monitoring was applied to data from a clinical study involving 14 female volunteers with normal menstrual cycles receiving testosterone via transdermal route, as to test its ability to detect testosterone administration. The study samples consisted of urine and blood collected during 4 weeks of a control phase and 4 weeks with a daily testosterone gel application. Integrating multiple biomarkers improved the detection of testosterone gel administration with substantially higher sensitivity compared with the distinct follow-up of each biomarker, when applied to selected urine and serum steroid biomarkers, as well as the combination of both. Among the 175 known positive samples, 38% were identified by the multimodal approach using urine biomarkers, 79% using serum biomarkers and 83% by combining biomarkers from both biological matrices, whereas 10%, 67% and 64% were respectively detected using standard unimodal monitoring. The detection of abnormal patterns can be improved using multimodal approaches. The combination of urine and serum biomarkers reduced the overall number of false-negatives, thus evidencing promising complementarity between urine and blood sampling for doping control, as highlighted in the case of the use of transdermal testosterone preparations. The generation in a multimodal setting of adaptive and personalized reference ranges opens up new opportunities in clinical and anti-doping profiling. The integration of multiple parameters in a longitudinal monitoring is expected to provide a more complete evaluation of individual profiles generating actionable intelligence to further guide sample collection, analysis protocols and decision-making in clinics and anti-doping

Performance of the new SPS beam position orbit system (MOPOS)

The orbit and trajectory measurement system COPOS of the CERN SPS accelerator has been in operation since the construction of the machine in 1976. Over the years the system has been slightly modified in order to follow the evolving demands of the machine, in particular for its operation as a p-pbar collider and, since 1991, for the acceleration of heavy ions. In 1995 the performance of the system was reviewed and the following shortcomings were identified: - lack of turn-by-turn position measurements due to the 1ms integration time of the voltage to frequency converters used for the analogue to digital conversion (to be compared with a revolution time of 23 ms), - ageing effects on the 200 MHz resonating input filters, which had over the years drifted out of tolerance. As a consequence the signal to noise ratio, the linearity and the absolute precision were affected, - the calibration system based on electromechanical relays had become very unreliable, such that frequent calibrations were no longer possible, - a remote diagnostic for the observation of timing signals relative to the beam signals was missing. For the above reasons a large-scale upgrade program was launched, the results of which are described in the following sections

Real time- and control software for the new orbit measurement system for the CERN SPS

The 240 channel SPS Orbit acquisition system is implemented on a PowerPC under the LynxOS operating system, making use of multi threaded real-time capabilities. The acquired data is transferred efficiently by DMA via the PCI bus into the main memory. System configuration aspects were implemented in a Broker architecture, where individual threads communicate with an Oracle database and the acquisition systems. This Broker hides the implementation details of the front-end systems. A versatile configuration client is provided in Java, to provide both local graphical user interfaces and remote WWW access using a dedicated gateway to the SL equipment layer. The timing diagnostics of the acquisition system are provided in a LabView application integrating oscilloscope control and channel multiplex control. This paper describes in detail the technical solutions implemented and reports on the arguments, which have led to particular choices

Toward Annealing Stable Molybdenum Oxide Based Hole Selective Contacts For Silicon Photovoltaics

Molybdenum oxide MoOX combines a high work function with broadband optical transparency. Sandwiched between a hydrogenated intrinsic amorphous silicon passivation layer and a transparent conductive oxide, this material allows a highly efficient hole selective front contact stack for crystalline silicon solar cells. However, hole extraction from the Si wafer and transport through this stack degrades upon annealing at 190 C, which is needed to cure the screen printed Ag metallization applied to typical Si solar cells. Here, we show that effusion of hydrogen from the adjacent layers is a likely cause for this degradation, highlighting the need for hydrogen lean passivation layers when using such metal oxide based carrier selective contacts. Pre MoOX deposition annealing of the passivating a Si H layer is shown to be a straightforward approach to manufacturing MoOX based devices with high fill factors using screen printed metallization cured at 190

Brainjacking: Implant Security Issues in Invasive Neuromodulation

The security of medical devices is critical to good patient care, especially when the devices are implanted. In light of recent developments in information security, there is reason to be concerned that medical implants are vulnerable to attack. The ability of attackers to exert malicious control over brain implants (“brainjacking”) has unique challenges that we address in this review, with particular focus on deep brain stimulation implants. To illustrate the potential severity of this risk, we identify several mechanisms through which attackers could manipulate patients if unauthorized access to an implant can be achieved. These include blind attacks in which the attacker requires no patient-specific knowledge and targeted attacks that require patient-specific information. Blind attacks include cessation of stimulation, draining implant batteries, inducing tissue damage, and information theft. Targeted attacks include impairment of motor function, alteration of impulse control, modification of emotions or affect, induction of pain, and modulation of the reward system. We also discuss the limitations inherent in designing implants and the trade-offs that must be made to balance device security with battery life and practicality. We conclude that researchers, clinicians, manufacturers, and regulatory bodies should cooperate to minimize the risk posed by brainjacking