Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study.

BACKGROUND: Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. METHODS: We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. RESULTS: Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. CONCLUSION: Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction.

Characterization of Biostable Atomic Layer Deposited (ALD) Multilayer Passivation Coatings for Active Implants.

The next generation of flexible, electrically active implants, such as brain implants or retina chips require a flexible, biostable as well as biocompatible passivation, ensuring a degradation-free usage for long time periods on the order of several years. Until today, these passivations are prepared mostly by polyimides or parylene, both of which are water vapor permeable to a certain degree. To remedy this deficiency, Atomic Layer Deposited (ALD) thin films are characterized regarding their electrical passivating features under conditions of accelerated aging, such as elevated temperatures in a liquid environment. The initial electrical passivation by various ALD deposited multilayers, combining alternating thin Al2O3 and TiO2 layers is the goal of this research as well as the stability of these layers under induced degradation. Such layers, in combination with a parylene passivation, would ensure a water vapor impermeable and biocompatible coating.

Mapping the electric field distribution of tightly focused cylindrical vector beams with gold nanorings.

In this paper gold nanorings (NRs) are applied as particularly well-suited sensing elements for mapping the radially symmetric electric fields in the high numerical aperture focus of cylindrical vector beams. The optical properties of gold nanorings are analyzed by a combination of extinction and single particle dark field spectroscopy as well as confocal photoluminescence (PL) imaging. The results are compared to numerical calculations. The in-plane components in the focus of the cylindrical vector beams are estimated through the PL intensity distributions of the NRs. The optimum overlap between the structure and excitation is visualized by a narrow centre spot in the far-field PL scan.

Compact plasmonic optical biosensors based on nanostructured gradient index lenses integrated into microfluidic cells.

We report on a compact and cost-effective integrated label-free biosensor configuration which is based on the refractive index sensitivity of the localized surface plasmon resonance (LSPR) of gold nanostructures. Aiming for compactification and miniaturization of the sensor, arrays of nanodiscs were fabricated on the planar surface of a gradient index (GRIN) lens, which acts as a substrate as well as an imaging objective for the light scattered by the gold structures. Integration of the lens into a microfluidic flow cell enabled the controlled exchange of liquid media at the sensor surface. The light scattered by the nanostructures was investigated spatially and spectrally resolved making use of the imaging properties of the GRIN lens. Dynamic spectral analysis during refractive index changes was conducted, revealing high sensitivities of up to 372 nm per refractive index unit for the shift of the LSPR. Biosensing capabilities were demonstrated by the detection of binding of an analyte by means of a testosterone-immunoassay.

Acute mobilization and migration of bone marrow-derived stem cells following anterior cruciate ligament rupture.

OBJECTIVE: Little is known regarding acute local and systemic processes following anterior cruciate ligament (ACL) rupture. No study has elucidated whether bone marrow-derived mesenchymal stem cells (MSCs) are mobilized into circulation and recruited to the injured joint. METHODS: In Part 1, Lewis rats were randomized to noninvasive ACL rupture (Rupture) or non-injured (Control) (n = 6/group). After 72 h, whole blood MSC concentration was assessed using flow cytometry. Synovial fluid and serum were assayed for stromal cell-derived factor (SDF)-1α and cartilage degeneration biomarkers, respectively. In Part 2, 12 additional rats were randomized and intravenously-injected with fluorescently-labeled allogenic MSCs. Cell tracking was performed using longitudinal, in vivo and ex vivo near-infrared (NIR) imaging and histology. Synovium SDF-1α and interleukin (IL)-17A immunostaining was performed. Serum was assayed for SDF-1α and 29 other cytokines. RESULTS: In Part 1, there was a significant increase in MSC concentration and synovial fluid SDF-1α in Rupture. No differences in cartilage biomarkers were observed. In Part 2, Rupture had significantly higher NIR signal at 24, 48, and 72 h, indicating active recruitment of MSCs to the injured joint. Ex vivo cell tracking demonstrated MSC localization in the synovium and myotendinous junction (MTJ) of the quadriceps. Injured synovia exhibited increased synovitis grade and higher degree of IL-17A and SDF-1α immunostaining. CONCLUSION: ACL rupture induced peripheral blood mobilization of MSCs and migration of intravenously-injected allogenic MSCs to the injured joint, where they localized in the synovium and quadriceps MTJ.

Determination of the strong coupling constant α s ( m Z ) in next-to-next-to-leading order QCD using H1 jet cross section measurements: H1 Collaboration.

The strong coupling constant α s is determined from inclusive jet and dijet cross sections in neutral-current deep-inelastic ep scattering (DIS) measured at HERA by the H1 collaboration using next-to-next-to-leading order (NNLO) QCD predictions. The dependence of the NNLO predictions and of the resulting value of α s ( m Z ) at the Z-boson mass m Z are studied as a function of the choice of the renormalisation and factorisation scales. Using inclusive jet and dijet data together, the strong coupling constant is determined to be α s ( m Z ) = 0.1157 ( 20 ) exp ( 29 ) th . Complementary, α s ( m Z ) is determined together with parton distribution functions of the proton (PDFs) from jet and inclusive DIS data measured by the H1 experiment. The value α s ( m Z ) = 0.1142 ( 28 ) tot obtained is consistent with the determination from jet data alone. The impact of the jet data on the PDFs is studied. The running of the strong coupling is tested at different values of the renormalisation scale and the results are found to be in agreement with expectations.

Transforming polyethylenimine into a pH-switchable hydrogel by additional supramolecular interactions.

Attaching a self-complementary zwitterionic supramolecular binding site to the amino groups of polyethyleneimine leads to a pH switchable hydrogel as dimerization of the zwitterions introduces additional crosslinks between the polymer chains. This gel responds to both the addition of either acid or base, as only the zwitterion can self-assemble but neither the protonated or deprotonated form.

Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro.

BACKGROUND: Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of this study were to determine the effect of two amide local anaesthetics, ropivacaine and bupivacaine, on methylation in two breast cancer cell lines and to detect whether the combination of lidocaine with the chemotherapy agent 5-aza-2'-deoxycytidine (DAC) would result in additive demethylating effects. METHODS: Breast cancer cell lines BT-20 [oestrogen receptor (ER)-negative] and MCF-7 (ER-positive) were incubated with lidocaine, bupivacaine, and ropivacaine to assess demethylating properties. Then, we tested varying concentrations of lidocaine and DAC to assess whether their demethylating effects were additive. Cell numbers and global methylation status were analysed. RESULTS: Lidocaine decreased methylation in BT-20 and MCF-7 cells, ropivacaine decreased methylation in BT-20 cells, and bupivacaine had no demethylating effect. When combined, lidocaine and DAC had additive demethylating effects. CONCLUSIONS: At clinically relevant doses, lidocaine and ropivacaine exert demethylating effects on specific breast cancer cell lines, but bupivacaine does not. The demethylating effects of lidocaine and DAC are indeed additive.

Performance of a fire detector based on a compact laser spectroscopic carbon monoxide sensor.

In this paper we show the suitability of a miniaturized tunable diode laser spectroscopy (TDLS)-based carbon-monoxide (CO) sensor for fire detection applications. The sensor utilizes a vertical-cavity surface-emitting laser (VCSEL) and inherent calibration scheme with reference gas filled in the photodetector housing. The fire-detection experiments are carried out under realistic conditions as described in the European standard EN54. The CO generation of all class C fires (according to EN54) could be well resolved. The cross-sensitivity to other substances was found to be very low: the maximum CO false response from cigarette smoke, hairspray and general aerosols reaches a low value of a few µL/L and only if the substance is directly applied into the sensor gas inlet. Therefore this sensor overcomes the disadvantage of high false alarm rate given by smoke detectors and is also in small size which is suitable for household and industrial applications. Hence, the VCSEL-based TDLS sensor is shown to have sufficient performance for fire-detection. It has advantages such as capability for fail-safe operation and, low cross-sensitivities as compared to existing point fire detector technology which is presently limited by these factors.

[Radiology in combination with hospital communication - challenges, solutions and pitfalls : radiology IT as important component of electronic patient records in the University Hospital Hamburg-Eppendorf (UKE)]. / Radiologie im Verbund der Klinikkommunikation - Herausforderungen, Lösungen und Fallstricke : Die Radiologie-IT als wichtiger Baustein der elektronischen Patientenakte im Universitätsklinikum Hamburg-Eppendorf (UKE).

BACKGROUND: Radiological information technology (IT) is nowadays one of many components of an integrated hospital IT structure. OBJECTIVE: This review article is concerned with the challenges of a comprehensive and complete integration of all documented information and communication of all medical disciplines in a hospital in the electronic patient records. Special attention is paid to the role of radiology and the interface between radiological and clinical systems. PERSPECTIVES: The utilization of the documented data paying special attention to the requirements of data protection is a core aim for the further development of electronic patient records in the University Hospital Hamburg-Eppendorf in the coming years.

[Colocutaneous fistula after a PEG procedure with introducer technique and gastropexy]. / Kolokutane Fistel nach PEG-Anlage mittels Introducer-Technik mit Gastropexie.

INTRODUCTION: The pull-PEG (percutaneous endoscopic gastrostomy) is the most commonly used procedure for PEG placement. Alternative methods may be used in patients with an obstructed oesophagus. We here present the case of an unusual complication during PEG placement with the new introducer technique and gastropexy. CASE REPORT: A 74-year-old men with progressive thymus cell carcinoma was referred for a PEG procedure. Since the tumour stenosis in the oesophagus was only passable with a slim-sight endoscope (5,9 mm), we decided in favour of the direct PEG method with gastropexy. The procedure was performed without any complications. 35 days later we changed the balloon catheter and were able to easily inflate the balloon. Surprisingly, the X-ray performed thereafter, revealed a misplacement of the catheter in the colon without any notable contrast medium in the stomach. Although the patient expressed no complaints, he underwent surgery on the same day proving the colocutaneous fistula. There were no signs of peritonitis. The patient's postoperative recovery was uneventful. DISCUSSION: Pull-PEG requires an intact oesophageal passage. The spread of bacteria and tumour cells is a possible risk factor. Direct punction PEG might be better in these cases. This method is not a standard procedure, but the recent implementation of an additional gastropexy represents a significant improvement. We experienced a rare complication, which was first described in 1987. However, this case is the first documented complication in association with gastropexy. This case shows that even gastropexy does not prevent colon interposition. Therefore, an endoscopic or radiological control of the tube placement after changing seems to be necessary.

Pulsed gate sweep strategies for hysteresis reduction in carbon nanotube transistors for low concentration NO(2) gas detection.

Carbon-nanotube-based field effect transistors (CNFETs) have been employed as highly sensitive chemical sensors. Often used as the sensor output signal, the gate threshold voltage (V(th)) is subject to concentration-dependent shifts upon exposure to target analytes. However, an unambiguous determination of the intrinsic V(th) is usually hampered by substantial hysteresis in CNFET gate characteristics. In this study we show that short gate voltage (V(gd)) pulses can be used for hysteresis reduction in CNFETs as chemical sensors, in particular for NO(2) detection. In the pulsed operation regime, even small shifts of V(th) upon sub-ppm NO(2) exposure remain resolvable. Furthermore, the hysteretic behaviour is systematically investigated by varying the pulse waveforms and timing parameters. Finally, we use an adapted hysteresis model for pulsed V(gd) and employ it to discuss the measurement data.

Tailoring gold nanostructures for near-field optical applications.

A method of combined thin-film deposition, electron beam lithography, and ion milling is presented for the fabrication of gold and silver nanostructures. The flexibility of lithographical processes for the variation of geometric parameters is combined with three-dimensional control over the surface evolution. Depending on the etching angle, different shapes ranging from cones over rods to cups can be achieved. These size- and shape-tunable structures present a toolbox for nano-optical investigations. As an example, optical properties of systematically varying structures are examined in a parabolic mirror confocal microscope.

Characterization of the morphology and composition of commercial negative resists used for lithographic processes.

We present a spectroscopic and microscopic characterization of the chemical composition, structure, and morphology of two commercial negative resists using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). For this purpose, films of a novolak-based resist (ma-N 2400) and hydrogen silsesquioxane (HSQ) are treated under different conditions (temperature, deep ultraviolet (DUV) exposure, CHF(3) plasma). Topographic AFM images show that both heating and DUV exposure strongly affect the surface morphology of as-prepared ma-N 2400 resist films. These different treatment conditions also lead to decreasing roughnesses, which indicates structural reorganization. Furthermore, the decrease of the photoactive compound (bisazide) in the ma-N 2400 resist films, observed in FTIR spectra, suggests cross-linking of the resist after CHF(3) plasma treatment, heating, or DUV exposure. XPS measurements on different CHF(3) plasma-treated surfaces reveal that a structurally homogeneous fluorine-containing polymer is generated that is responsible for an enhanced etch resistance. FTIR measurements of HSQ films show a correlation between the degree of HSQ cross-linking and baking time.

[Physical urticaria]. / Physikalische Urtikaria.

The different types of physical urticaria are triggered by mechanical and thermal stimuli, as well as electromagnetic waves. Localized forms restricted to the skin and mucous membranes are most common, but generalized urticaria with variable extracutaneous manifestations can also occur. Physical urticaria is usually sporadic but may rarely have a familial form; it is often associated with chronic urticaria. In most instances, the short time interval between the physical stimulus and reaction points to a causal relationship, but in delayed types the exact diagnosis may be missed without provocation tests. The clinical implication of physical urticaria is demonstrated by investigations showing a greater degree of disability in affected patients as compared to other types of urticaria. There is still an incomplete understanding of the crucial pathophysiological aspects; most likely inflammatory reactions involving leukocytes, endothelial cells and nerves stimulated by various mediators play an important role in this form of urticaria.

The influence of atracurium, cisatracurium, and mivacurium on the proliferation of two human cell lines in vitro.

We tested the influence of atracurium and cisatracurium (final concentrations: 0, 0.96, 3.2, 9.6, 32, and 96 microM) on proliferation of human cells (hepatoma HepG2 cells and human umbilical vein endothelial cells) in vitro. In additional experiments, glutathione, N-acetylcysteine, or carboxyl esterase was added before the addition of either relaxant. The number of cells counted after 72 h of incubation was expressed as a percentage of the mean cell number in wells incubated without additives. Atracurium and cisatracurium progressively decreased cell proliferation in a concentration-dependent pattern. With human umbilical vein endothelial cells, atracurium or cisatracurium (3.2 microM) decreased the cell count to 67.7 % (SD, 14.8%) and 50% (SD, 8.6%), respectively. Cell proliferation was not inhibited by mivacurium. The results were similar to those with HepG2 cells. Glutathione, N-acetylcysteine, and carboxyl esterase partially reversed the effects of atracurium and cisatracurium. When incubated in a buffer with glutathione, atracurium decreased the number of glutathione-sulfhydryl groups. The findings that atracurium and cisatracurium inhibit proliferation of human cell lines in vitro, but that mivacurium does not, and that this effect is alleviated by glutathione and N-acetylcysteine, as well as by the carboxyl esterase, indicate that the inhibition may be caused by the reactive acrylate metabolites.

Theoretical limits of scanning white-light interferometry signal evaluation algorithms.

Scanning white-light interferometry is widely used for the microstructure analysis of technical and biological specimens. For each pixel in the focal plane of the apparatus a white-light interferogram is acquired and evaluated by means of an algorithm. We discuss some properties of mathematically optimal evaluation methods and the best possible achievable resolution derived therefrom depending on the setup parameters. A comparison of the results to one of the algorithms described in the literature is given.