Terahertz (THz) fields are widely used for sensing, communication and quality control. In future applications, they could be efficiently confined, enhanced and manipulated well below the classical ...diffraction limit through the excitation of graphene plasmons (GPs). These possibilities emerge from the strongly reduced GP wavelength, λ
, compared with the photon wavelength, λ
, which can be controlled by modulating the carrier density of graphene via electrical gating. Recently, GPs in a graphene/insulator/metal configuration have been predicted to exhibit a linear dispersion (thus called acoustic plasmons) and a further reduced wavelength, implying an improved field confinement, analogous to plasmons in two-dimensional electron gases (2DEGs) near conductive substrates. Although infrared GPs have been visualized by scattering-type scanning near-field optical microscopy (s-SNOM), the real-space imaging of strongly confined THz plasmons in graphene and 2DEGs has been elusive so far-only GPs with nearly free-space wavelengths have been observed. Here we demonstrate real-space imaging of acoustic THz plasmons in a graphene photodetector with split-gate architecture. To that end, we introduce nanoscale-resolved THz photocurrent near-field microscopy, where near-field excited GPs are detected thermoelectrically rather than optically. This on-chip detection simplifies GP imaging as sophisticated s-SNOM detection schemes can be avoided. The photocurrent images reveal strongly reduced GP wavelengths (λ
≈ λ
/66), a linear dispersion resulting from the coupling of GPs with the metal gate below the graphene, and that plasmon damping at positive carrier densities is dominated by Coulomb impurity scattering.
Low serum albumin levels resulting from inflammation-induced capillary leakage or disease-related anorexia during acute illness are associated with poor outcomes. We investigated the relationship of ...nutritional status and inflammation with low serum albumin levels and 30-day mortality in a large cohort.
We prospectively enrolled adult patients in the medical emergency department of a Swiss tertiary care center and investigated associations of C-reactive protein (CRP) and Nutritional Risk Screening 2002 as markers of inflammation and poor nutritional status, respectively, with low serum albumin levels and mortality using multivariate regression analyses.
Among the 2465 patients, 1019 (41%) had low serum albumin levels (<34 g/L), 619 (25.1%) had increased nutritional risk (Nutritional Risk Screening 2002 ≥3), and 1086 (44.1%) had CRP values >20 mg/L. Multivariate analyses adjusted for age, gender, diagnosis, and comorbidities revealed elevated CRP values (adjusted odds ratio OR 10.51, 95% confidence interval, 7.51-14.72, P <.001) and increased malnutrition risk (adjusted OR 2.87, 95% confidence interval, 1.98-4.15, P <.001) to be associated with low serum albumin levels, even adjusting for both parameters. Low serum albumin levels, elevated CRP values, and increased nutritional risk independently predicted 30-day mortality, with areas under the curve of 0.77, 0.70, and 0.75, respectively. Combination of these 3 parameters showed an area under the curve of 0.82 to predict mortality.
Elevated parameters of inflammation and high nutritional risk were independently associated with hypoalbuminemia. All 3 parameters independently predicted mortality. Combining them during initial evaluation of patients in emergency departments facilitates mortality risk stratification.
Abstract Objective The aim of this study was to examine the prevalence of nutritional risk and its association with multiple adverse clinical outcomes in a large cohort of acutely ill medical ...inpatients from a Swiss tertiary care hospital. Methods We prospectively followed consecutive adult medical inpatients for 30 d. Multivariate regression models were used to investigate the association of the initial Nutritional Risk Score (NRS 2002) with mortality, impairment in activities of daily living (Barthel Index <95 points), hospital length of stay, hospital readmission rates, and quality of life (QoL; adapted from EQ5 D); all parameters were measured at 30 d. Results Of 3186 patients (mean age 71 y, 44.7% women), 887 (27.8%) were at risk for malnutrition with an NRS ≥3 points. We found strong associations (odds ratio/hazard ratio OR/HR, 95% confidence interval CI) between nutritional risk and mortality (OR/HR, 7.82; 95% CI, 6.04–10.12), impaired Barthel Index (OR/HR, 2.56; 95% CI, 2.12–3.09), time to hospital discharge (OR/HR, 0.48; 95% CI, 0.43–0.52), hospital readmission (OR/HR, 1.46; 95% CI, 1.08–1.97), and all five dimensions of QoL measures. Associations remained significant after adjustment for sociodemographic characteristics, comorbidities, and medical diagnoses. Results were robust in subgroup analysis with evidence of effect modification ( P for interaction < 0.05) based on age and main diagnosis groups. Conclusion Nutritional risk is significant in acutely ill medical inpatients and is associated with increased medical resource use, adverse clinical outcomes, and impairments in functional ability and QoL. Randomized trials are needed to evaluate evidence-based preventive and treatment strategies focusing on nutritional factors to improve outcomes in these high-risk patients.
To investigate the aqueous humor proteome in patients with glaucoma and a control group.
Aqueous humor was obtained from five human donors diagnosed with primary open angle glaucoma (POAG) and five ...age- and sex-matched controls undergoing cataract surgery. Quantitative proteome analysis of the aqueous humor by hyper reaction monitoring mass spectrometry (HRM-MS) based on SWATH technology was performed.
Expression levels of 87 proteins were found to be different between glaucomatous and control aqueous humor. Of the 87 proteins, 34 were significantly upregulated, whereas 53 proteins were downregulated in the aqueous humor from glaucoma patients compared to controls. Differentially expressed proteins were found to be involved in cholesterol-related, inflammatory, metabolic, antioxidant as well as proteolysis-related processes.
Glaucoma leads to profound changes to the aqueous humor proteome consistent with an altered metabolic state, an inflammatory response and impaired antioxidant defense.
Abstract Background hepatitis C infections are detected by anti-HCV screening tests. Reactive anti-HCV results give no information about the presence or absence of hepatitis C viruses, or of ...unspecific reactivity. To obtain information about the viral load, HCV RNA measurements, following a reactive anti-HCV result, are performed in well equipped and specialised laboratories. Anti-HCV immunoblots are the only means to exclude non specific reactivity. The measurement of HCV core antigen (HCV-Ag), as an alternative to HCV RNA, is discussed, as it can be analysed on the same instrument as anti-HCV. Objectives The detection limit of HCV-Ag is crucial to use it in lieu of HCV RNA, in regard of the different genotypes. A renewed algorithm is proposed to exclude unspecific reactivity of anti-HCV. Study designs Samples were tested on Architect i2000SR (Abbott) for anti-HCV and HCV-Ag. HCV RNA measurements were obtained by Cobas Ampliprep/Taqman (Roche) or m2000rt® (Abbott). Results and Conclusions Comparison between HCV-Ag and HCV RNA from 126 samples of 101 patients with chronic hepatitis C gave linear regression R2 0.89, slope 0.885 and intercept −2.258, which were independent of the genotypes. The detection limit of HCV-Ag was between 2.4 and 4.5 Log10 IU/mL. A renewed algorithm for confirmation of reactive anti-HCV results is proposed: active or resolved hepatitis C infections or false reactivity can be differentiated by sequenced reflex testing due to HCV-Ag, anti-HCV immunoblot and HCV RNA.
•Simultaneous and fast detection of phosphatidylcholine-derived metabolites.•Applicable for EDTA-plasma, serum and urine samples.•High accuracy and precision.
The determination of circulating ...trimethylamine-N-oxide (TMAO), choline, betaine, l-carnitine and O-acetyl-l-carnitine concentration in different human matrices is of great clinical interest. Recent results highlighted the prognostic value of TMAO and quaternary ammonium containing metabolites in the field of cardiovascular and kidney diseases. Herein, we report a method for the rapid and simultaneous measurement of closely related phosphatidylcholine-derived metabolites in three different biological matrices by stable isotope dilution assay. Plasma, serum and urine samples were simply deproteinized and separated by HILIC-chromatography. Detection and quantification were performed using LC–MS/MS with electrospray ionization in positive mode. For accuracy and precision, full calibration was performed covering more than the full reference range. Assay performance metrics include intra- and interday imprecision were below 10% for all analytes. To exclude matrix effects standard addition methods were applied for all matrices. It was shown that calibration standards and quality control prepared in water can be used instead of matrix-matched calibration and controls. The LC/MS/MS-based assay described in this article may improve future clinical studies evaluating TMAO and related substances as prognostic markers for cardiovascular risk and all-cause mortality in different patient populations.
Summary Background The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but ...screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. Methods ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. Findings With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 1·58–1·69 including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). Interpretation In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Funding Each centre had its own funding responsibility.
As LC–MS/MS techniques are becoming more accessible even outside of highly specialized clinical laboratories, pre-analytical issues such as drug stability during specimen storage should be critically ...evaluated before implementing therapeutic drug monitoring. Our study investigated the influence of physico-chemical properties of different drugs in regard to their interaction with gel separators used in commercial available collection tubes.
Drug spiked blood samples were analyzed after storage in different commercial gel- and non-gel based serum tubes. LC–ESI–MS/MS based methods were used to determine drug concentration in serum samples.
Lipophilic compounds, defined by logP>3 and a compatibility factor>20 are prone to be efficiently and rapidly absorbed by lipophilic gel barriers inducing a significant in-vitro decrease of drug concentration over a short storage time. Our data show a relevant drop of concentration of posaconazole, sertraline and citalopram when stored in gel based tubes. Molecular descriptors such as logP, polar surface area and protein binding seem to be good predictive markers to identify gel interacting drugs.
For ease of handling and minimization of blood drawing times, we assume that tubes containing separator gel can be used for therapeutic drug monitoring of high hydrophilic drugs. In contrast lipophilic compounds showing logP higher than 3 and/or CF>20 should be critically considered and validated by extensive stability studies.
Abbreviations: logP, partition coefficient; PSA, polar surface area; TDM, therapeutic drug monitoring; ACN, acetonitrile; MeOH, methanol; IVD, in-vitro diagnostic; CF, compatibility factor
•Physico-chemical properties of drugs influence the adsorption to the gel barrier.•LogP, PSA and protein binding seems to be good predictive markers.•Drugs showing a logP>3 should be critically reviewed.•Tubes with mechanical separator can prevent interaction between drug und gel layer.
PDF
