[The new Parkinson's disease pain classification system (PD-PCS)]. / Die neue Parkinson-Schmerzklassifikation (PSK).

BACKGROUND: Chronic pain is a common non-motor symptom in patients with Parkinson's disease (PD). AIM: To facilitate the diagnosis of pain in PD, we developed a new classification system the Parkinson's disease pain classification system (PD-PCS) and translated the corresponding validated questionnaire into German. METHODS: A causal relationship of the respective pain syndrome with PD can be determined by four questions before assigning it hierarchically into one of three pain categories (neuropathic, nociceptive and nociplastic). RESULTS: In the initial validation study 77% of the patients (122/159) had PD-associated pain comprising 87 (55%) with nociceptive, 36 (22%) with nociplastic and 24 (16%) with neuropathic pain. The study revealed a high validity of the questionnaire and a moderate intrarater and interrater reliability. The questionnaire has been adapted into German and employed in 30 patients. DISCUSSION: The PD-PCS questionnaire is a valid and reliable tool to determine the relationship of a pain syndrome with PD before classifying it according to the underlying category, facilitating further diagnostics and treatment.

Optical efficiency and gain dynamics of modelocked semiconductor disk lasers.

Compact optically pumped passively modelocked semiconductor disk lasers (SDLs) based on active quantum wells (QWs) such as vertical external-cavity surface-emitting lasers (VECSELs) or modelocked integrated external-cavity surface-emitting lasers (MIXSELs) are wavelength-versatile sources that offer a unique combination of gigahertz pulse repetition rates and short pulse durations. In this paper, we present record-short pulses of 184 fs from a gigahertz MIXSEL emitting at a center wavelength of 1048 nm. This result comes at the expense of low optical-to-optical pump efficiency (<1%) and average output power limited to 115 mW. We experimentally observe that shorter pulses significantly reduce the macroscopic gain saturation fluence and develop a QW model based on rate equations to reproduce the gain saturation behavior and quantitatively explain the VECSEL and MIXSEL modelocking performances. We identify spectral hole burning as the main cause of the reduced gain at shorter pulse durations, which in combination with the short lifetime of the excited carriers strongly reduces the optical pump efficiency. Our better understanding will help to address these limitations in future ultrafast SDL designs.

Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic hypotension in Parkinson's disease - a randomized controlled trial.

BACKGROUND AND PURPOSE: Evidence for effective treatment options for orthostatic hypotension (OH) in Parkinson's disease (PD) is scarce. Elevation of cholinergic tone with pyridostigmine bromide has been reported as a way to improve blood pressure (bp) regulation in neurogenic hypotension without causing supine hypertension. METHODS: This was a double-centre, double-blind, randomized, active-control, crossover, phase II non-inferiority trial of pyridostigmine bromide for OH in PD (clinicaltrials.gov NCT01993680). Patients with confirmed OH were randomized to 14 days 3 × 60 mg/day pyridostigmine bromide or 1 × 0.2 mg/day fludrocortisone before crossover. Outcome was measured by peripheral and central bp monitoring during the Schellong manoeuvre and questionnaires. RESULTS: Thirteen participants were enrolled between April 2013 and April 2015 with nine participants completing each trial arm. Repeated measures comparison showed a significant 37% improvement with fludrocortisone for the primary outcome diastolic bp drop on orthostatic challenge (baseline 22.9 ± 13.6 vs. pyridostigmine bromide 22.1 ± 17.0 vs. fludrocortisone 14.0 ± 12.6 mmHg; P = 0.04), whilst pyridostigmine bromide had no effect. Fludrocortisone caused an 11% peripheral systolic supine bp rise (baseline 128.4 ± 12.8 vs. pyridostigmine bromide 130.4 ± 18.3 vs. fludrocortisone 143.2 ± 10.1 mmHg; P = 0.01) but no central mean arterial supine bp rise (baseline 107.2 ± 7.8 vs. pyridostigmine bromide 97.0 ± 12.0 vs. fludrocortisone 107.3 ± 6.3 mmHg; P = 0.047). Subjective OH severity, motor score and quality of life remained unchanged by both study interventions. CONCLUSIONS: Pyridostigmine bromide is inferior to fludrocortisone in the treatment of OH in PD. This trial provides first objective evidence of the efficacy of 0.2 mg/day fludrocortisone for OH in PD, causing minor peripheral but no central supine hypertension. In addition to peripheral bp, future trials should include central bp measurements, known to correlate more closely with cardiovascular risk.

Structural and Electronic Properties of Nitrogen-Doped Graphene.

We investigate the structural and electronic properties of nitrogen-doped epitaxial monolayer graphene and quasifreestanding monolayer graphene on 6H-SiC(0001) by the normal incidence x-ray standing wave technique and by angle-resolved photoelectron spectroscopy supported by density functional theory simulations. With the location of various nitrogen species uniquely identified, we observe that for the same doping procedure, the graphene support, consisting of substrate and interface, strongly influences the structural as well as the electronic properties of the resulting doped graphene layer. Compared to epitaxial graphene, quasifreestanding graphene is found to contain fewer nitrogen dopants. However, this lack of dopants is compensated by the proximity of nitrogen atoms at the interface that yield a similar number of charge carriers in graphene.

Self-reference in psychosis and depression: a language marker of illness.

BACKGROUND: Language use is of increasing interest in the study of mental illness. Analytical approaches range from phenomenological and qualitative to formal computational quantitative methods. Practically, the approach may have utility in predicting clinical outcomes. We harnessed a real-world sample (blog entries) from groups with psychosis, strong beliefs, odd beliefs, illness, mental illness and/or social isolation to validate and extend laboratory findings about lexical differences between psychosis and control subjects. METHOD: We describe the results of two experiments using Linguistic Inquiry and Word Count software to assess word category frequencies. In experiment 1, we compared word use in psychosis and control subjects in the laboratory (23 per group), and related results to subject symptoms. In experiment 2, we examined lexical patterns in blog entries written by people with psychosis and eight comparison groups. In addition to between-group comparisons, we used factor analysis followed by clustering to discern the contributions of strong belief, odd belief and illness identity to lexical patterns. RESULTS: Consistent with others' work, we found that first-person pronouns, biological process words and negative emotion words were more frequent in psychosis language. We tested lexical differences between bloggers with psychosis and multiple relevant comparison groups. Clustering analysis revealed that word use frequencies did not group individuals with strong or odd beliefs, but instead grouped individuals with any illness (mental or physical). CONCLUSIONS: Pairing of laboratory and real-world samples reveals that lexical markers previously identified as specific language changes in depression and psychosis are probably markers of illness in general.

Tracking Primary Thermalization Events in Graphene with Photoemission at Extreme Time Scales.

Direct and inverse Auger scattering are amongst the primary processes that mediate the thermalization of hot carriers in semiconductors. These two processes involve the annihilation or generation of an electron-hole pair by exchanging energy with a third carrier, which is either accelerated or decelerated. Inverse Auger scattering is generally suppressed, as the decelerated carriers must have excess energies higher than the band gap itself. In graphene, which is gapless, inverse Auger scattering is, instead, predicted to be dominant at the earliest time delays. Here, <8 fs extreme-ultraviolet pulses are used to detect this imbalance, tracking both the number of excited electrons and their kinetic energy with time-and angle-resolved photoemission spectroscopy. Over a time window of approximately 25 fs after absorption of the pump pulse, we observe an increase in conduction band carrier density and a simultaneous decrease of the average carrier kinetic energy, revealing that relaxation is in fact dominated by inverse Auger scattering. Measurements of carrier scattering at extreme time scales by photoemission will serve as a guide to ultrafast control of electronic properties in solids for petahertz electronics.

Detection of nickel and palladium contact hypersensitivity by a flow cytometric lymphocyte proliferation test.

We established a flow cytometric lymphocyte proliferation test (LPT) for the detection of nickel (Ni) and palladium (Pd) sensitization. Eighty-one consecutive patients with an indication for patch test (PT) were tested by LPT with Ni (NiSO4 ) and Pd (Na2 PdCl4 and PdCl2 ) salts. The imprecision of the LPT was low (coefficient of variation 7.2%). Using PT as a diagnostic reference, the sensitivity and specificity of LPT were 74.4% and 80% for NiSO4 , 74.4% and 78.3% for Na2 PdCl4 , and 57.2% and 85.4% for PdCl2 , respectively. For both Ni and Pd, the likelihood ratio for a positive PT markedly increased with increasing LPT value. With medical history as a reference, the sensitivity and specificity were 40.6% and 82.1% for LPT and 59.4% and 89.7% for PT, respectively. Combination of LPT and PT resulted in a higher specificity of 95%, albeit lower sensitivity of 34.4%. In conclusion, flow cytometric LPT represents a reliable and useful method for the detection of Ni and Pd sensitization. LPT values correlate with PT results and, when used in combination with PT, increase test specificity.

Word use in first-person accounts of schizophrenia.

BACKGROUND: Language use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights. AIMS: To test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia. METHOD: Word counting software was applied to first-person accounts of schizophrenia and mood disorder. RESULTS: More third-person plural pronouns ('they') and fewer first-person singular pronouns ('I') were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts. CONCLUSIONS: Differences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.

Ubiquitous defect-induced density wave instability in monolayer graphene.

Quantum materials are notoriously sensitive to their environments, where small perturbations can tip a system toward one of several competing ground states. Graphene hosts a rich assortment of such competing phases, including a bond density wave instability ("Kekulé distortion") that couples electrons at the K/K' valleys and breaks the lattice symmetry. Here, we report observations of a ubiquitous Kekulé distortion across multiple graphene systems. We show that extremely dilute concentrations of surface atoms (less than three adsorbed atoms every 1000 graphene unit cells) can self-assemble and trigger the onset of a global Kekulé density wave phase. Combining complementary momentum-sensitive angle-resolved photoemission spectroscopy (ARPES) and low-energy electron diffraction (LEED) measurements, we confirm the presence of this density wave phase and observe the opening of an energy gap. Our results reveal an unexpected sensitivity of the graphene lattice to dilute surface disorder and show that adsorbed atoms offer an attractive route toward designing novel phases in two-dimensional materials.

Probing a century old prediction one plasmonic particle at a time.

In 1908, Gustav Mie solved Maxwell's equations to account for the absorption and scattering of spherical plasmonic particles. Since then much attention has been devoted to the size dependent optical properties of metallic nanoparticles. However, ensemble measurements of colloidal solutions generally only yield the total extinction cross sections of the nanoparticles. Here, we show how Mie's prediction on the size dependence of the surface absorption and scattering can be probed separately for the same gold nanoparticle by using two single particle spectroscopy techniques, (1) dark-field scattering and (2) photothermal imaging, which selectively only measure scattering and absorption, respectively. Combining the optical measurements with correlated scanning electron microscopy furthermore allowed us to measure the size of the spherical gold nanoparticles, which ranged from 43 to 274 nm in diameter. We found that even though the trend predicted by Mie theory is followed well by the experimental data over a large range of nanoparticle diameters, for small size variations changes in scattering and absorption intensities are dominated by factors other than those considered by Mie theory. In particular, spectral shifts of the plasmon resonance due to deviations from a spherical particle shape alone cannot explain the observed variation in absorption and scattering intensities.

Room temperature strain-induced Landau levels in graphene on a wafer-scale platform.

Graphene is a powerful playground for studying a plethora of quantum phenomena. One of the remarkable properties of graphene arises when it is strained in particular geometries and the electrons behave as if they were under the influence of a magnetic field. Previously, these strain-induced pseudomagnetic fields have been explored on the nano- and micrometer-scale using scanning probe and transport measurements. Heteroepitaxial strain, in contrast, is a wafer-scale engineering method. Here, we show that pseudomagnetic fields can be generated in graphene through wafer-scale epitaxial growth. Shallow triangular nanoprisms in the SiC substrate generate strain-induced uniform fields of 41 T, enabling the observation of strain-induced Landau levels at room temperature, as detected by angle-resolved photoemission spectroscopy, and confirmed by model calculations and scanning tunneling microscopy measurements. Our work demonstrates the feasibility of exploiting strain-induced quantum phases in two-dimensional Dirac materials on a wafer-scale platform, opening the field to new applications.

[Three-dimensional echocardiography in cardiac surgery. Current status and perspectives]. / Klinischer Einsatz der 3D-Echokardiographie in der Herzchirurgie. Aktueller Stand und Perspektiven.

Three-dimensional (3D) echocardiography is a new imaging technique that can provide useful information about cardiovascular morphology, pathology, and function. Recent refinements in instrumentation, data acquisition, post-processing, and computation speed allow 3D echocardiography to play an important role in cardiac imaging. These modalities provide comprehensive information on ventricular and valve morphology and function. Combined with 3D color Doppler sonography, further assessment of valvular function and determination of flow in the left ventricular outflow tract and cross-septal defects are now possible. Three-dimensional color flow imaging also makes echocardiography accurate for assessing the severity of mitral regurgitation. The purpose of this review is to describe technical developments in 3D echocardiography and its clinical application in cardiac surgery. Moreover, based on clinical studies at our centre, we describe the morphology of the mitral valve, its flow pattern, and function of the mitral annulus.

Dual-comb spectroscopy of water vapor with a free-running semiconductor disk laser.

Dual-comb spectroscopy offers the potential for high accuracy combined with fast data acquisition. Applications are often limited, however, by the complexity of optical comb systems. Here we present dual-comb spectroscopy of water vapor using a substantially simplified single-laser system. Very good spectroscopy measurements with fast sampling rates are achieved with a free-running dual-comb mode-locked semiconductor disk laser. The absolute stability of the optical comb modes is characterized both for free-running operation and with simple microwave stabilization. This approach drastically reduces the complexity for dual-comb spectroscopy. Band-gap engineering to tune the center wavelength from the ultraviolet to the mid-infrared could optimize frequency combs for specific gas targets, further enabling dual-comb spectroscopy for a wider range of industrial applications.

LPS directly induces oxygen radical production in human monocytes via LPS binding protein and CD14.

In human monocytes, superoxide (O2-) generation accompanies phagocytosis and is important for bactericidal activity. It also contributes to tissue damage in inflammation. In the present study we investigated, whether lipopolysaccharide (LPS) directly stimulates monocyte O2- production with kinetics known for other LPS effects and, if so, by which mechanism. LPS caused a time- and dose-dependent O2- release in nonadherent purified monocytes. The effect appeared after 5 min, peaked at 30 min, and disappeared after 2 h. It was maximal with 10 ng/ml lipid A (+148 +/- 22%, P < .001), 1 ng/ml LPS Escherichia coli Re (+226 +/- 68%, P < .001), and 100 ng/ml LPS Salmonella abortus equi sm (+272 +/- 52%, P < .001), respectively. The effect was not observed in buffer, even when using 10 micrograms/ml LPS. It was dependent on the presence of heat-inactivated AB serum, with a maximal effect at > or = 0.5%. Serum could be replaced by LPS-binding protein (LBP). Polymyxin B and anti-LBP antiserum, respectively, blocked the LPS effect. LPS-induced O2- generation was also completely blocked by anti-CD14 antibodies (3C10 and 63D3) and by their corresponding F(ab')2 fragments. Monocytes treated with phosphoinositol-specific phospholipase C and monocytes from patients with paroxysmal nocturnal hemoglobinuria, lacking the phosphatidylinositol-anchored CD14, did not respond to LPS stimulation with O2- production. Similarly to LPS, E. coli caused stronger O2- production with heat-inactivated serum than without, and this effect was blocked by anti-CD14 antibodies. In conclusion, these data indicate that LPS directly stimulates O2- production in human monocytes via CD14 depending on LBP.

Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy.

Monocyte phenotypes and functions were studied in 22 patients with major depression, and compared with those of 22 matched healthy controls. Immune measures were performed before and after dexamethasone suppression, and after 4 and 12 weeks of moclobemide therapy in patients. Seven patients terminated after 4 weeks because of treatment failure; 11 out of 15 patients responded to therapy after 12 weeks. Monocyte human leukocyte antigen class II and CD14 antigen expression, tumor necrosis factor production, and plasma interferon-gamma and neopterin did not differ in patients before treatment and controls. The reaction to dexamethasone was also similar in patients and controls. Neither antidepressive treatment per se nor the clinical response to it affected any immunological parameter. In conclusion, corticosteroid-controlled monocyte functions were similar in untreated and treated depressed patients and in controls, and unrelated to the clinical course of the disease.

CO2 fluxes of cryptogamic crusts: II. Response to dehydration.

The carbon dioxide exchange of Microcoleus- and Scytonema-dominated cryptogamic crusts as related to dehydration was measured in the laboratory with a modified discrete sampling technique and infrared gas analysis. The dehydration curves predicted that carboxylation and dark respiration rates for both crust types would become zero at from 4 to 5% water content (W) (approximately 16-23% soil saturation), with the water contents at which the rates became zero significantly lower in the second treatment cycle than the first. The dehydration curves predicted that net photosynthesis rates would become zero at 6.7-11.2% W (27-44% soil saturation), with the water contents at which the rates became zero significantly higher in the second cycle of treatment than the first.

CO2 fluxes of cryptogamic crusts: I. Response to resaturation.

The relationship between carbon dioxide exchange of Microcoleus- and Scytonema-dominated cryptogamic crusts and resaturation time was measured in the laboratory with a modified discrete sampling technique and infrared gas analysis. Maximum net photosynthetic rate of Microcoleus was 187 nmol CO2 m-2 s-1 and of Scytonema was 111 nmol CO2 m-2 s-1 for rehydration to 100% soil saturation. Both crust types demonstrated a slow rise in resaturation respiration and took 2 days to become fully active after the (first rehydration to 100% soil saturation after long-term dryness, and only one day to become active after the second rehydration cycle.

Selective inhibition of bacterial dihydroorotate dehydrogenases by thiadiazolidinediones.

Dihydroorotate dehydrogenase is a critical enzyme of de novo pyrimidine biosynthesis in prokaryotic and eukaryotic cells. Differences in the primary structure of the enzymes from Gram-positive and -negative bacteria and from mammals indicate significant structural divergence among these enzymes. We have identified a class of small molecules, the thiadiazolidinediones, that inhibit prototypical enzymes from Gram-positive and -negative bacteria, but are inactive against the human enzyme. The most potent compound in our collection functioned as a time-dependent irreversible inactivator of the bacterial enzymes with k(inact)/K(i) values of 48 and 500 M(-1) sec(-1) for the enzymes from Escherichia coli and Enterococcus faecalis, respectively. The data presented here indicate that it is possible to inhibit prokaryotic dihydroorotate dehydrogenases selectively while sparing the mammalian enzyme. Thus, this enzyme may represent a valuable target for the development of novel antibiotic compounds.

Chlorinated hydrocarbons in women with repeated miscarriages.

This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases.

Percutaneous epidural and nerve root block and percutaneous lumbar sympatholysis.

Epidural steroid injections and selective nerve root blocks currently are considered standard techniques in the diagnosis and treatment of back pain. The targeted epidural and perineural steroid injection with nerve block is a new technique that combines an epidural steroid injection and a nerve block. Radiologists are best suited for performing these procedures because of their training and skills in fluoroscopy and needle procedures.