Quantum \v{C}erenkov Radiation: Spectral Cutoffs and the Role of Spin and Orbital Angular Momentum

We show that the well-known \v{C}erenkov Effect contains new phenomena arising from the quantum nature of charged particles. The \v{C}erenkov transition amplitudes allow coupling between the charged particle and the emitted photon through their orbital angular momentum (OAM) and spin, by scattering into preferred angles and polarizations. Importantly, the spectral response reveals a discontinuity immediately below a frequency cutoff that can occur in the optical region. Specifically, with proper shaping of electron beams (ebeams), we predict that the traditional \v{C}erenkov radiation angle splits into two distinctive cones of photonic shockwaves. One of the shockwaves can move along a backward cone, otherwise considered impossible for \v{C}erenkov radiation in ordinary matter. Our findings are observable for ebeams with realistic parameters, offering new applications including novel quantum optics sources, and open a new realm for \v{C}erenkov detectors involving the spin and orbital angular momentum of charged particles.Comment: 27 pages, 3 figure

The trail making test as a screening instrument for driving performance in older drivers; a translational research.

BACKGROUND: In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients' on-road driving performance in the context of cognitive decline. METHODS: This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers' licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance. RESULTS: The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%. CONCLUSION: In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors

Colloid-stabilized emulsions: behaviour as the interfacial tension is reduced

We present confocal microscopy studies of novel particle-stabilized emulsions. The novelty arises because the immiscible fluids have an accessible upper critical solution temperature. The emulsions have been created by beginning with particles dispersed in the single-fluid phase. On cooling, regions of the minority phase nucleate. While coarsening these nuclei become coated with particles due to the associated reduction in interfacial energy. The resulting emulsion is arrested, and the particle-coated interfaces have intriguing properties. Having made use of the binary-fluid phase diagram to create the emulsion we then make use of it to study the properties of the interfaces. As the emulsion is re-heated toward the single-fluid phase the interfacial tension falls and the volume of the dispersed phase drops. Crumpling, fracture or coalescence can follow. The results show that the elasticity of the interfaces has a controlling influence over the emulsion behaviour.Comment: Submitted for the proceedings of the 6th Liquid Matter Conference, held in Utrecht (NL) in July 200

2OACTIVATION OF T CELLS UPON TREATMENT WITH BISPECIFIC ANTIBODIES CORRELATES WITH THE EXPRESSION OF CO-INHIBITORY RECEPTORS ON TUMOR-INFILTRATING LYMPHOCYTES IN HUMAN LUNG CANCER

Introduction: T cell bispecific antibodies (TCB) are designed to recruit and simultaneously activate T cells against target cells such as tumor cells expressing a particular surface antigen. However, it is currently unknown how immuno-modulatory mechanisms active in the tumor microenvironment such as the expression of T cell co-inhibitory receptors may influence the therapeutic effect of TCBs. Methods: We performed a comprehensive phenotypic analysis of tumor infiltrating immune cells from lung carcinoma digests by multicolour flow cytometry. In particular, expression of T cell co-inhibitory and -stimulatory receptors was analyzed. Tumor digests were treated with catumaxomab, a TCB directed against CD3 and EpCAM. T cell activation and effector functions were assessed upon exposure to catumaxomab. Results: CD8+ T cells in lung carcinoma showed a broad heterogeneity in expression of the T cell co-inhibitory receptors PD-1, Tim-3, CTLA-4, Lag-3 and BTLA. Tumor stage and nodal status correlated with number and intensity of expressed receptors. Upon exposure to catumaxomab, a considerable heterogeneity in T cell activation among different tumors was observed. Of note, T cells expressing high levels and multiple co-inhibitory receptors were more impaired in their activation and effector functions after treatment with catumaxomab indicating a higher level of exhaustion. In a further analysis of CD8+ TIL subsets we found that BTLA+ T cells expressed more additional inhibitory receptors than all other subsets, namely PD-1, Tim-3, CTLA-4 and Lag-3, whereas only a small part of PD-1+ T cells expressed another receptor. Tim-3+ T cells usually co-expressed PD-1, but multiple receptors were found only on a low number of cells. Conclusion: In summary, our data suggest that the activity of TCBs is largely affected by the expression of T cell co-inhibitory receptors on tumor-infiltrating immune cells. Furthermore, these data provide a clinical rationale for combining bispecific antibodies with compounds which antagonize T cell exhaustion. Disclosure: D. Thommen, J. Schreiner, P. Herzig, P. Mueller and A. Zippelius: received research funding from Roche Glycart; V. Karanikas: is employed by Roche Glycart. All other authors have declared no conflicts of interes

Medication incidents in primary care medicine: protocol of a study by the Swiss Federal Sentinel Reporting System.

BACKGROUND/RATIONALE: Patient safety is a major concern in healthcare systems worldwide. Although most safety research has been conducted in the inpatient setting, evidence indicates that medical errors and adverse events are a threat to patients in the primary care setting as well. Since information about the frequency and outcomes of safety incidents in primary care is required, the goals of this study are to describe the type, frequency, seasonal and regional distribution of medication incidents in primary care in Switzerland and to elucidate possible risk factors for medication incidents. Label="METHODS AND ANALYSIS" ="METHODS"/> <AbstractText STUDY DESIGN AND SETTING: We will conduct a prospective surveillance study to identify cases of medication incidents among primary care patients in Switzerland over the course of the year 2015. PARTICIPANTS: Patients undergoing drug treatment by 167 general practitioners or paediatricians reporting to the Swiss Federal Sentinel Reporting System. INCLUSION CRITERIA: Any erroneous event, as defined by the physician, related to the medication process and interfering with normal treatment course. EXCLUSION CRITERIA: Lack of treatment effect, adverse drug reactions or drug-drug or drug-disease interactions without detectable treatment error. PRIMARY OUTCOME: Medication incidents. RISK FACTORS: Age, gender, polymedication, morbidity, care dependency, hospitalisation. STATISTICAL ANALYSIS: Descriptive statistics to assess type, frequency, seasonal and regional distribution of medication incidents and logistic regression to assess their association with potential risk factors. Estimated sample size: 500 medication incidents. LIMITATIONS: We will take into account under-reporting and selective reporting among others as potential sources of bias or imprecision when interpreting the results. ETHICS AND DISSEMINATION: No formal request was necessary because of fully anonymised data. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT0229537

ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures

ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available

CO2 isotope sensor using a broadband infrared source, a spectrally narrow 4.4 μm quantum cascade detector, and a Fourier spectrometer

We report a prototype CO2 gas sensor based on a simple blackbody infrared source and a spectrally narrow quantum cascade detector (QCD). The detector absorption spectrum is centered at 2260cm−1 (4.4μm) and has a full width at half maximum of 200cm−1 (25meV). It covers strong absorption bands of two spectrally overlapping CO2 isotopomers, namely the P-branch of 12CO2 and the R-branch of 13CO2. Acquisition of the spectral information and data treatment were performed in a Fourier transform infrared (FTIR) spectrometer. By flushing its sample compartment either with nitrogen, dry fresh air, ambient air, or human breath, we were able to determine CO2 concentrations corresponding to the different gas mixtures. Adetection limit of 500ppb was obtained in these experiment