Fourier-transform THz spectroscopy based on electric-field interferometry using THz-PMT.

We demonstrate a high dynamic range (DR) Fourier-transform-based terahertz (THz) spectrometer by combining a THz photomultiplier tube (PMT) with a metasurface and a conventional Michelson interferometer. Because the THz-PMT response depends on the incident electric-field strength following the Fowler-Nordheim equation, we can directly obtain an electric field interferogram without any synchronized optical probe pulse in contrast to conventional THz-time-domain-spectroscopy (THz-TDS). The DR of the corresponding power spectrum using the proposed method was 4.6 × 105 without the use of a lock-in amplifier. The complex refractive index of a quartz glass plate obtained using the proposed method was in good agreement with the results of conventional THz-TDS.

Establishment of primary prostate epithelial and tumorigenic cell lines using a non-viral immortalization approach.

BACKGROUND: Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro. Epithelial cells can be immortalized, accomplished by using viral integration of immortalization factors. Viral approaches, however, might be impaired by regulatory and safety issues as well as random integration into regulatory genetic elements, modifying precise gene expression. We intend to use surgical specimen of prostate cancer patients to (i) prove for establishment of cancer cell lines, and (ii) perform non-viral, Sleeping Beauty (SB) transposase-based immortalization of prostate epithelial cells. METHODS: Radical prostatectomy samples of prostate cancer patients (n = 4) were dissociated and cultured in vitro. Cells were cultivated either without or after non-viral, Sleeping-Beauty transposase-based stable transfection with immortalization factors SV40LT and hTERT. Established cell lines were analyzed in vitro and in vivo for characteristics of prostate (cancer) cells. RESULTS: Initial cell cultures without genetic manipulation underwent senescence within ≤ 15 passages, demonstrating inability to successfully derive primary prostate cancer cell lines. By using SB transposase-based integration of immortalization factors, we were able to establish primary prostate cell lines. Three out of four cell lines displayed epithelial characteristics, however without expression of prostate (cancer) characteristics, e.g., androgen receptor. In vivo, one cell line exhibited tumorigenic potential, yet characteristics of prostate adenocarcinoma were absent. CONCLUSION: Whereas no primary prostate cancer cell line could be established, we provide for the first-time immortalization of primary prostate cells using the SB transposase system, thereby preventing regulatory and molecular issues based on viral immortalization approaches. Although, none of the newly derived cell lines demonstrated prostate cancer characteristics, tumor formation was observed in one cell line. Given the non-prostate adenocarcinoma properties of the tumor, cells have presumably undergone oncogenic transformation rather than prostate cancer differentiation. Still, these cell lines might be used as a tool for research on prostate cancer initiation and early cancer progression.

Terahertz Cross-Correlation Spectroscopy and Imaging of Large-Area Graphene.

We demonstrate the use of a novel, integrated THz system to obtain time-domain signals for spectroscopy in the 0.1-1.4 THz range. The system employs THz generation in a photomixing antenna excited by a broadband amplified spontaneous emission (ASE) light source and THz detection with a photoconductive antenna by coherent cross-correlation sampling. We benchmark the performance of our system against a state-of-the-art femtosecond-based THz time-domain spectroscopy system in terms of mapping and imaging of the sheet conductivity of large-area graphene grown by chemical vapor deposition (CVD) and transferred to a PET polymer substrate. We propose to integrate the algorithm for the extraction of the sheet conductivity with the data acquisition, thereby enabling true in-line monitoring capability of the system for integration in graphene production facilities.

Non-Contact Paper Thickness and Quality Monitoring Based on Mid-Infrared Optical Coherence Tomography and THz Time Domain Spectroscopy.

In industrial paper production, online monitoring of a range of quality parameters is essential for ensuring that the performance and appearance of the final product is suitable for a given application. In this article, two optical sensing techniques are investigated for non-destructive, non-contact characterization of paper thickness, surface roughness, and production defects. The first technique is optical coherence tomography based on a mid-infrared supercontinuum laser, which can cover thicknesses from ~20-90 µm and provide information about the surface finish. Detection of subsurface voids, cuts, and oil contamination was also demonstrated. The second technique is terahertz time domain spectroscopy, which is used to measure paper thicknesses of up to 443 µm. A proof-of-concept thickness measurement in freely suspended paper was also demonstrated. These demonstrations highlight the added functionality and potential of tomographic optical sensing methods towards industrial non-contact quality monitoring.

The effect of economic development on population health: a review of the empirical evidence.

Background: Economic growth is considered an important determinant of population health. Sources of data: Relevant studies investigating the effect of economic growth on health outcomes were identified from Google Scholar and PubMed searches in economics and medical journals. Areas of agreement: Additional resources generated through economic growth are potentially useful for improving population health. Areas of controversy: The empirical evidence on the aggregate effect of economic growth on population health is rather mixed and inconclusive. Growing points: The causal pathways from economic growth to population health are crucial and failure or success in completing the pathways explains differences in empirical findings. Areas timely for developing research: Future research should investigate how additional resources can more effectively reach those in need and how additional resources can be used more efficiently. It is particularly relevant to understand why preventive health care in developing countries is very price elastic whereas curative health care is very health inelastic and how this understanding can inform public health policy.

Leadership in moving human groups.

How is movement of individuals coordinated as a group? This is a fundamental question of social behaviour, encompassing phenomena such as bird flocking, fish schooling, and the innumerable activities in human groups that require people to synchronise their actions. We have developed an experimental paradigm, the HoneyComb computer-based multi-client game, to empirically investigate human movement coordination and leadership. Using economic games as a model, we set monetary incentives to motivate players on a virtual playfield to reach goals via players' movements. We asked whether (I) humans coordinate their movements when information is limited to an individual group member's observation of adjacent group member motion, (II) whether an informed group minority can lead an uninformed group majority to the minority's goal, and if so, (III) how this minority exerts its influence. We showed that in a human group--on the basis of movement alone--a minority can successfully lead a majority. Minorities lead successfully when (a) their members choose similar initial steps towards their goal field and (b) they are among the first in the whole group to make a move. Using our approach, we empirically demonstrate that the rules of swarming behaviour apply to humans. Even complex human behaviour, such as leadership and directed group movement, follow simple rules that are based on visual perception of local movement.

Effects of Short-Term Gluten-Free Diet on Cardiovascular Biomarkers and Quality of Life in Healthy Individuals: A Prospective Interventional Study.

INTRODUCTION: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world's population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons. AIM AND METHODS: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink®) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated. RESULTS: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed. CONCLUSION: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.

Vascular dysfunction and arterial hypertension in experimental celiac disease are mediated by gut-derived inflammation and oxidative stress.

AIMS: We examined the cardiovascular effects of celiac disease (CeD) in a humanized mouse model, with a focus on vascular inflammation, endothelial dysfunction, and oxidative stress. METHODS AND RESULTS: NOD.DQ8 mice genetically predisposed to CeD were subjected to a diet regime and oral gavage to induce the disease (gluten group vs. control). We tested vascular function, confirmed disease indicators, and evaluated inflammation and oxidative stress in various tissues. Plasma proteome profiling was also performed. CeD markers were confirmed in the gluten group, indicating increased blood pressure and impaired vascular relaxation. Pro-inflammatory genes were upregulated in this group, with increased CD11b+ myeloid cell infiltration and oxidative stress parameters observed in aortic and heart tissue. However, heart function remained unaffected. Plasma proteomics suggested the cytokine interleukin-17A (IL-17A) as a link between gut and vascular inflammation. Cardiovascular complications were reversed by adopting a gluten-free diet. CONCLUSION: Our study sheds light in the heightened cardiovascular risk associated with active CeD, revealing a gut-to-cardiovascular inflammatory axis potentially mediated by immune cell infiltration and IL-17A. These findings augment our understanding of the link between CeD and cardiovascular disease providing clinically relevant insight into the underlying mechanism. Furthermore, our discovery that cardiovascular complications can be reversed by a gluten-free diet underscores a critical role for dietary interventions in mitigating cardiovascular risks associated with CeD.

Data File Standard for Flow Cytometry, version FCS 3.1.

The flow cytometry data file standard provides the specifications needed to completely describe flow cytometry data sets within the confines of the file containing the experimental data. In 1984, the first Flow Cytometry Standard format for data files was adopted as FCS 1.0. This standard was modified in 1990 as FCS 2.0 and again in 1997 as FCS 3.0. We report here on the next generation flow cytometry standard data file format. FCS 3.1 is a minor revision based on suggested improvements from the community. The unchanged goal of the standard is to provide a uniform file format that allows files created by one type of acquisition hardware and software to be analyzed by any other type.The FCS 3.1 standard retains the basic FCS file structure and most features of previous versions of the standard. Changes included in FCS 3.1 address potential ambiguities in the previous versions and provide a more robust standard. The major changes include simplified support for international characters and improved support for storing compensation. The major additions are support for preferred display scale, a standardized way of capturing the sample volume, information about originality of the data file, and support for plate and well identification in high throughput, plate based experiments. Please see the normative version of the FCS 3.1 specification in Supporting Information for this manuscript (or at http://www.isac-net.org/ in the Current standards section) for a complete list of changes.

Establishment of primary prostate epithelial and tumorigenic cell lines using a non-viral immortalization approach

Background Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro. Epithelial cells can be immortalized, accomplished by using viral integration of immortalization factors. Viral approaches, however, might be impaired by regulatory and safety issues as well as random integration into regulatory genetic elements, modifying precise gene expression. We intend to use surgical specimen of prostate cancer patients to (i) prove for establishment of cancer cell lines, and (ii) perform nonviral, Sleeping Beauty (SB) transposase-based immortalization of prostate epithelial cells. Methods Radical prostatectomy samples of prostate cancer patients (n = 4) were dissociated and cultured in vitro. Cells were cultivated either without or after non-viral, Sleeping-Beauty transposase-based stable transfection with immortalization factors SV40LT and hTERT. Established cell lines were analyzed in vitro and in vivo for characteristics of prostate (cancer) cells. Results Initial cell cultures without genetic manipulation underwent senescence within ≤ 15 passages, demonstrating inability to successfully derive primary prostate cancer cell lines. By using SB transposase-based integration of immortalization factors, we were able to establish primary prostate cell lines. Three out of four cell lines displayed epithelial characteristics, however without expression of prostate (cancer) characteristics, e.g., androgen receptor. In vivo, one cell line exhibited tumorigenic potential, yet characteristics of prostate adenocarcinoma were absent. Conclusion Whereas no primary prostate cancer cell line could be established, we provide for the first-time immortalization of primary prostate cells using the SB transposase system, thereby preventing regulatory and molecular issues based on viral immortalization approaches. Although, none of the newly derived cell lines demonstrated prostate cancer characteristics, tumor formation was observed in one cell line. Given the non-prostate adenocarcinoma properties of the tumor, cells have presumably undergone oncogenic transformation rather than prostate cancer differentiation. Still, these cell lines might be used as a tool for research on prostate cancer initiation and early cancer progression.

European Society of Intensive Care Medicine statement: intensive care medicine in Europe--structure, organisation and training guidelines of the Multidisciplinary Joint Committee of Intensive Care Medicine (MJCICM) of the European Union of Medical Specialists (UEMS).

This article describes the structures and institutions in the European Union by which professional training and qualification in medical specialities will be harmonised. All main medical specialities are represented in the European Union of Medical Specialists (UEMS) by speciality sections. For intensive care medicine, as a multidisciplinary speciality, a new structure of a Multidisciplinary Joint Committee of Intensive Care Medicine (MJCICM) within the UEMS was established in 1999. In this MJCICM the European Society of Intensive Care Medicine and the European Society of Paediatric and Neonatal Intensive Care are represented by delegates without voting capacity in a Standing Advisory Board. Statements and recommendations which the MJCICM has worked out until now are presented: Definitions of intensive care medicine, structural conditions for education and training, continuing medical education, criteria for accreditation of intensive care medicine training centres, common core curriculum for optional specialist training in intensive care medicine, as well as an intensive care units accreditation visiting programme and standards for medical treatment and nursing care.

Dexmedetomidine decreases perioperative myocardial lactate release in dogs.

UNLABELLED: The sympatholytic effect of the alpha(2)-adrenergic agonist dexmedetomidine may decrease emergence-related myocardial ischemic load in patients. However, a direct measure of myocardial ischemia, such as myocardial lactate release, is difficult to obtain in patients. Therefore, we studied mongrel dogs and measured myocardial lactate release, myocardial oxygen supply, hemodynamic variables, and neurohumoral indices of the stress response. After the induction of a standardized degree of borderline myocardial ischemia, either dexmedetomidine (dexmed group, n = 9) or normal saline (control group, n = 9) was infused. Measurements were repeated at the end of the anesthetic period and every 10 min during the 90-min emergence period. In the dexmed group, the cumulative emergence-related lactate release was 46% less than in the control group (95% confidence interval, 20%-80%; P = 0.02). Simultaneously, dexmedetomidine increased the endo-/epicardial blood flow ratio by 35% (control group, 0.4 +/- 0.1; dexmed group, 0.6 +/- 0.1; P = 0.03). These antiischemic effects of dexmedetomidine were accompanied by reduced plasma concentrations of norepinephrine (126 versus 577 pg/mL) and epinephrine (158 versus 1909 pg/mL) and a slower heart rate (123 +/- 6 versus 160 +/- 10 bpm, dexmed versus control). The antiischemic effect of dexmedetomidine started before emergence, as evidenced by a decreased prevalence of myocardial lactate release at that time (zero of eight dogs in the dexmed group and four of seven dogs in the control group had lactate release before emergence; P = 0.03). IMPLICATIONS: Dexmedetomidine decreases plasma catecholamines and heart rate during emergence from anesthesia. In dogs with a coronary stenosis, these sympatholytic effects decrease myocardial lactate release and, therefore, minimize emergence-related myocardial ischemia.

Efficacy and safety of remifentanil in coronary artery bypass graft surgery: a randomized, double-blind dose comparison study.

OBJECTIVES: To compare the efficacy and safety of 3 doses of remifentanil as part of a total intravenous anesthesia technique with low-dose propofol in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Multicenter, multinational, double-blind, randomized, dose comparison study. SETTING: Nine hospitals in 5 countries. PARTICIPANTS: One hundred forty-one patients undergoing first-time elective CABG surgery. INTERVENTIONS: Patients were premedicated with a short-acting oral benzodiazepine up to 2 h before surgery and randomized to receive continuous infusions of remifentanil 1.0 microg/kg/min (n = 45), 1.5 microg/kg/min (n = 44), or 2.0 microg/kg/min (n = 43), in combination with propofol 3 mg/kg/h. Nine patients received remifentanil 1.0 microg/kg/min on an open-label basis. Three different induction sequences (IS) were used. In IS 1 (n = 31), induction was started with remifentanil infusion followed 5 minutes later by propofol 0.5 mg/kg bolus and infusion at 3 mg/kg/h. Further bolus doses of propofol (10 mg) were given if loss of consciousness (LOC) was not attained after 5 minutes; pancuronium, 0.04 to 0.1 mg/kg, was administered at LOC. In IS 2 (n = 68), a priming dose of pancuronium, 0.015 mg/kg, was administered just before starting remifentanil. In IS 3 (n = 42), bolus doses of propofol, 10 mg every 10 seconds, were given until LOC, followed by pancuronium, 0.04 to 0.1 mg/kg, and the remifentanil and propofol infusions were started. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among the remifentanil dose groups with regard to the primary outcome measure, responses to sternotomy/sternal spread/maximal sternal spread. Responses to these stimuli were recorded in 11%, 11%, and 14% of patients in the remifentanil 1.0, 1.5, and 2.0 microg/kg/min dose groups, respectively. Similarly, there were no significant differences in the responses to other surgical stimuli. There was a high incidence of muscle rigidity when remifentanil was used to induce anesthesia. CONCLUSIONS: All 3 remifentanil dose regimens provided profound suppression of responses to surgical stimuli in the majority of patients. There was no apparent advantage in starting the remifentanil infusion rate above 1.0 microg/kg/min. Remifentanil is not suitable for use as a sole induction agent.