Application of light scattering tomography for Si(111) samples.

The detection of bulk micro-defects in Czochralski-grown silicon (Si) 〈100〉 wafers has significant importance in wafer quality control. Light Scattering Tomography (LST) is an industry standard technique for this purpose. This optical non-contact metrology requires destructive sample preparation: Samples have to be cleaved into half. One particular feature of the method is a dark field detection arrangement, which is achieved by separating the light detection part (microscope unit) from the illumination. Illumination is applied to the front surface of the sample, and the light scattered off of the defects is collected via the cleaved surface. The technique requires the perpendicularity of the cleaved surface to the front surface, which is fulfilled for Si(100) wafers. However, the nominally cleaved surface for Si(111) wafers is not perpendicular to the front surface but has an angle of 70.5°. This significant difference in cleavage results in the fact that Si(111) wafers cannot be measured by standard LST systems. Fortunately, the standard LST system can be modified by tilting the detection part under a proper angle allowing the measurements of Si(111) samples. In this article, we present this new technique in detail, showing the design and measurement capability of the new system. The measurement results are validated by a direct comparison to standard LST measurements on the same samples after proper sample preparation.

Bulk micro-defect detection with low-angle illumination.

The detection of oxygen precipitates, voids, and other defects is critical for semiconductor wafer makers. One of the industry standard techniques for detecting these Bulk Micro-Defects (BMDs) is Semilab's Light Scattering Tomograph (LST) system. In this measurement, unpatterned wafers are nominally cleaved in half. Illumination is applied to the front surface of the sample, and the light scattered off of the defects is collected via the cleaved surface. This technique had been limited to the measurement of unpatterned wafers, but device makers show significant interest in measuring BMD distributions on patterned wafers using scattering-based techniques. A pattern on the surface of the wafer can cause significant scattering, making the standard LST technique unsuitable for this task. We present a solution for patterned wafer BMD measurements by an addition of a low-angle illumination unit to the standard LST system. This new illumination unit focuses the light into the bulk of the wafer via the cleaved surface, which enables measurement on patterned samples. The new system is called "light scattering tomograph enhanced by low-angle illumination." Excellent correlation was found between the detected defect densities obtained by the low-angle and the standard LST illumination mode.

Differentiating sepsis from similar groups of symptoms at triage level in emergency care.

OBJECTIVES: Conditions that have similar initial presentations as sepsis may make early recognition of sepsis in an emergency room (ER) difficult. We investigated whether selected physiologic and metabolic parameters can be reliably used in the emergency department to differentiate sepsis from other disease states that mimic it, such as dehydration and stroke. METHODS: Loess regression on retrospective follow-up chart data of patients with sepsis-like symptoms (N = 664) aged 18+ in a large ER in Hungary was used to visualize/identify cutoff points for sepsis risk. A multivariate logistic regression model based on standard triage data was constructed with its corresponding receiver operating characteristic (ROC) curve and compared with another model constructed based on current sepsis guidelines. RESULTS: Age, bicarbonate, HR, lactate, pH, and body temperature had U, V, W, or reverse U-shaped associations with identifiable inflexion points, but the cutoff values we identified were slightly different from guideline cutoff values. In contrast to the guidelines, no inflexion points could be observed for the association of sepsis with SBP, DPB, MAP, and RR and therefore were treated as continuous variables. Compared to the guidelines-based model, the triage data-driven final model contained additional variables (age, pH, bicarbonate) and did not include lactate. The data-driven model identified about 85% of sepsis cases correctly, while the guidelines-based model identified only about 70% of sepsis cases correctly. CONCLUSION: Our findings contribute to the growing body of evidence for the necessity of finding improved tools to identify sepsis at early time points, such as in the ER.

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Pressure-induced switching properties of the iron(iii) spin-transition complex [FeIII(3-OMeSalEen)2]PF6.

We investigated the effect of an externally applied pressure on the iron(iii) Schiff-base compound [Fe(3-OMeSalEen)2]PF6 (H-3-OMeSalEen, condensation product of 3-methoxy-substituted salicylaldehyde and N-ethylethylenediamine), which at ambient pressure displays a thermal spin transition with a 3 K wide hysteresis loop centered at 164 K. Raman spectrometry revealed the occurrence of a complete spin-state switching process for a pressure of P1/2 = 8-9 kbar at room temperature. The evolution of lattice parameters as a function of pressure was followed by X-ray diffraction measurements on single crystals, highlighting the important microscopic aspects at the origin of the pressure-induced transition, i.e. an anisotropic response and a high compressibility of the HS molecular lattice. Variable temperature magnetic susceptibility measurements at different applied pressures revealed the smoothening of the spin transition curves and a linear increase of the transition temperatures by ca. 16.4 (1.0) K kbar-1, in good agreement with the Clausius-Clapeyron law. The non-negligible influence of the pressure transmitting oils on the intrinsic transition properties was also evidenced and attributed to mechanical interactions between the particles and the solidified matrix.

Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing.

In multiple myeloma malignant plasma cells expand within the bone marrow. Since this site is well-perfused, a rapid dissemination of "fitter" clones may be anticipated. However, an imbalanced distribution of multiple myeloma is frequently observed in medical imaging. Here, we perform multi-region sequencing, including iliac crest and radiology-guided focal lesion specimens from 51 patients to gain insight into the spatial clonal architecture. We demonstrate spatial genomic heterogeneity in more than 75% of patients, including inactivation of CDKN2C and TP53, and mutations affecting mitogen-activated protein kinase genes. We show that the extent of spatial heterogeneity is positively associated with the size of biopsied focal lesions consistent with regional outgrowth of advanced clones. The results support a model for multiple myeloma progression with clonal sweeps in the early phase and regional evolution in advanced disease. We suggest that multi-region investigations are critical to understanding intra-patient heterogeneity and the evolutionary processes in multiple myeloma.In multiple myeloma, malignant cells expand within bone marrow. Here, the authors use multi-region sequencing in patient samples to analyse spatial clonal architecture and heterogeneity, providing novel insight into multiple myeloma progression and evolution.

Elastic coupling between spin-crossover particles and cellulose fibers.

Composite materials made of cellulose fibers and spin crossover micro-particles were investigated by magnetic measurements and dynamic mechanical analysis (DMA). The storage modulus of the cellulose handsheet (0.6 GPa at room T) is significantly enhanced in the composite (1.7 GPa). The latter also displays a reversible increase of ca. 10% when switching the magnetic spin state of the particles from the low spin (LS) to the high spin (HS) form. Around the spin transition temperature a loss modulus peak is also observed, highlighting the strong viscoelastic coupling between the particles and the cellulose matrix. These results pave the way for the development of a novel family of actuator materials based on spin crossover-polymer composites.

Vasodilator Effect of Glucagon: Receptorial Crosstalk Among Glucagon, GLP-1, and Receptor for Glucagon and GLP-1.

Glucagon is known for its insulin-antagonist effect in the blood glucose homeostasis, while it also reduces vascular resistance. The mechanism of the vasoactive effect of glucagon has not been studied before; thereby we aimed to investigate the mediators involved in the vasodilatation induced by glucagon. The vasoactive effect of glucagon, insulin, and glucagon-like peptide-1 was studied on isolated rat thoracic aortic rings using a wire myograph. To investigate the mechanism of the vasodilatation caused by glucagon, we determined the role of the receptor for glucagon and the receptor for GLP-1, and studied also the effect of various inhibitors of gasotransmitters, inhibitors of reactive oxygen species formation, NADPH oxidase, prostaglandin synthesis, protein kinases, potassium channels, and an inhibitor of the Na(+)/Ca(2+)-exchanger. Glucagon causes dose-dependent relaxation in the rat thoracic aorta, which is as potent as that of insulin but greater than that of GLP-1 (7-36) amide. Vasodilatation by GLP-1 is partially mediated by the glucagon receptor. The vasodilatation due to glucagon evokes via the glucagon-receptor, but also via the receptor for GLP-1, and it is endothelium-independent. Contribution of gasotransmitters, prostaglandins, the NADPH oxidase enzyme, free radicals, potassium channels, and the Na(+)/Ca(2+)-exchanger is also significant. Glucagon causes dose-dependent relaxation of rat thoracic aorta in vitro, via the receptor for glucagon and the receptor for GLP-1, while the vasodilatation evoked by GLP-1 also evolves partially via the receptor for glucagon, thereby, a possible crosstalk between the 2 hormones and receptors could occur.

Enhanced luminescence stability with a Tb-spin crossover nanocomposite for spin state monitoring.

[Fe(Htrz)2(trz)]BF4@SiO2 nanorods were synthesized using a reverse emulsion technique and a Tb(3+) complex was chemically bound to the silica surface. This Tb-spin crossover nanocomposite demonstrates high luminescence stability under continuous thermal cycling. A reabsorption mechanism is determined to be responsible for the luminescence intensity variation during the spin state switching of the iron complex.

Nanocrystals of Fe(phen)2(NCS)2 and the size-dependent spin-crossover characteristics.

We report on the size reduction of the neutral Fe(phen)2(NCS)2 prototypical compound exhibiting a cooperative spin-crossover associated with a first-order phase transition (at ca. 176 K). We use the [Fe(phen)3](NCS)2 ionic precursor and the solvent-assisted precipitation technique to prepare an array of crystalline objects with sizes varying over two orders of magnitude (from 15 up to 1400 nm). TEM, X-ray diffraction and IR measurements provide evidences for the formation of particles of neutral and ionic species, which results from the interplay between the relevant chemical equilibrium and the reaction kinetics (ligand extraction, complex precipitation), and the modulation of the latter by physico-chemical parameters. A thermal transformation of diamagnetic nanocrystals of [Fe(phen)3](NCS)2 leads to spin-crossover particles of Fe(phen)2(NCS)2 of a comparable size. Powders of nano-, micro- and polycrystals of Fe(phen)2(NCS)2 present X-ray diffractograms typical of the so-called polymorph II. The importance of size effects on the cooperative spin-crossover process was probed with magnetic, Mössbauer, Raman and IR spectroscopic measurements. Each sample exhibits spin-state switching of the Fe(ii) ions. The salient features are: a cooperativity preserved at the micrometric scale, a very limited downshift of the transition temperature and an asymmetric spreading of the thermal process (over ca. 100 K) with the size reduction. At temperatures close to room temperature, the process appears to be quasi complete whatever the size of the samples. This result, extracted from Raman data, was confirmed by Mössbauer measurements in the case of the largest objects (LS residue <5-10% for bulk and microparticles). Below 150 K, a very efficient low-spin to high-spin photoexcitation was induced by the Raman laser beam in all the samples which prevents the extraction of the high-spin fraction in this temperature range. However variable temperature IR spectra of the 29 nm particles indicate that the HS residue, that is close to zero in the case of microparticles, does not drastically increase (<30%) for the smallest particles. The processing of a number of related spin-crossover compounds in the form of nanoparticles may be achieved with this general approach.

Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation.

Previous studies have shown that in diabetes mellitus, insulin-induced relaxation of arteries is impaired and the level of ortho-tyrosine (o-Tyr), an oxidized amino acid is increased. Thus, we hypothesized that elevated vascular level of o-Tyr contributes to the impairment of insulin-induced vascular relaxation. Rats were fed with o-Tyr for 4 weeks. Insulin-induced vasomotor responses of isolated femoral artery were studied using wire myography. Vascular o-Tyr content was measured by HPLC, whereas immunoblot analyses were preformed to detect eNOS phosphorylation. Sustained oral supplementation of rats with o-Tyr increased the content of o-Tyr in the arterial wall and significantly reduced the relaxations to insulin. Sustained supplementation of cultured endothelial cells with o-Tyr increased the incorporation of o-Tyr and mitigated eNOS Ser (1 177) phosphorylation to insulin. Increasing arterial wall o-Tyr level attenuates insulin-induced relaxation - at least in part - by decreasing eNOS activation. Elevated level of o-Tyr could be an underlying mechanism for vasomotor dysfunction in diabetes mellitus.

Increase in insulin-induced relaxation of consecutive arterial segments toward the periphery: Role of vascular oxidative state.

RATIONALE: The oxidative state has been implicated in the signaling of various vasomotor functions, yet its role regarding the vasomotor action of insulin is less known. OBJECTIVE: To investigate the insulin-evoked relaxations of consecutive arterial segments of different oxidative state and the role of extracellular signal-regulated kinase (ERK) pathway. METHODS AND RESULTS: The oxidative state, as assessed by the level of ortho-tyrosine, was higher in the thoracic aorta of rats than in the abdominal aorta, and was the lowest in the femoral artery. The vasomotor function of vessels of same origin was studied using a small-vessel myograph. Insulin-induced relaxations increased toward the periphery (i.e., thoracic < abdominal < femoral). Aortic banding and hydrogen peroxide/aminotriazole increased the oxidative state of the thoracic aorta that was accompanied by ERK activation and decreased relaxation to insulin, and vice versa, acutely lowered oxidative state by superoxide dismutase/catalase improved relaxation. In contrast, insulin-induced relaxation of the femoral artery could be enhanced with a higher oxidative state, and reduced with a lower state. CONCLUSIONS: Oxidative state of vessels modulates the magnitude of vasomotor responses to insulin, which appears to be mediated via the ERK signaling pathway.

[Transanal endoscopic microsurgery--our initial experience]. / Chirurgia transanala endoscopica--experienta noastra initiala.

UNLABELLED: The aim of this study was to describe a single institution's experience with transanal endoscopic microsurgery (TEMS) in patients with benign and malignant rectal tumors. MATERIAL AND METHOD: This was a prospective descriptive survey. Between January 2006 and January 2010, 14 patients underwent transanal endoscopic microsurgery excision of benign (8) or malignant (6) rectal tumors, located 4 to 15 cm from the dentate line. Median age was 59.7 years and the mean follow up was 29 months. RESULTS: The average tumor size was 3.4 cm, median operating time was 40 min. Median length of hospital stay was 4.35 days. During the follow-up period, benign tumor recurrence was observed in one patient (7.14%), managed by repeated TEMS. Histologic staging of malignant tumors was T1 (2) and T2 (4). In two patients with inadequate resection margins open radical surgery was performed. One had recurrent disease, which was managed by radical surgery. No cancer-related deaths were observed during the follow-up period. There was no operative mortality. No major postoperative complications were recorded. Anal incontinence persisted for 3 weeks in one patient. CONCLUSION: Transanal endoscopic microsurgery excision is a safe and precise technique and should become a procedure of choice for benign rectal tumors and selected early malignant neoplasms.

Formation of nanoparticles by ion beam irradiation of thin films.

The possibility of fabricating nanoparticles by ion bombardment was investigated by the ion bombardment of indium films on oxide covered Si and Cr surfaces. The different masses of implanting specimen ensured the different energy transfer while the same Si substrate ensured the same thermal conductivity for the In and Cr layers. Chromium served as a reference for the effect of ion bombardment and as a substrate as well. The SRIM program was used to simulate the ion surface interaction process. The nanoparticles were detected by scanning electron microscopy (SEM). We found that the melting of the In layer results in the formation of nanoparticles of 50-300 nm diameter and 5-10 nm height. This method can be promising for nanoparticle formation of materials with low melting point.

Effects of erythropoietin on glucose metabolism.

We purposed to determine the impact of erythropoietin on altering glucose metabolism in the settings of in vitro and in vivo experiments. The acute effect of erythropoietin on lowering blood glucose levels was studied in animal experiments. In [³H]-deoxy-D-glucose isotope studies we measured glucose uptake with insulin and erythropoietin using 3T3-L1 cells cultured under normal or high glucose conditions. Altered activation of Akt and ERK pathways was evaluated in immunoblot analyses. Immunocytochemistry was conducted to determine the glucose transporter 4 translocation to the plasma membrane. Addition of erythropoietin significantly lowered blood glucose levels in vivo in rats. The glucose uptake was markedly increased by erythropoietin treatment (at concentrations 0.15, 0.3, and 0.625 ng/ml) in adipocytes grown in high glucose medium (p<0.05), but it remained unaltered in cells under normal glucose conditions. Significant increase of phosphorylation of ERK and Akt was detected due to erythropoietin (p<0.05). Co-administration of erythropoietin and insulin resulted in higher phosphorylation of Akt and [³H]-deoxy-D-glucose uptake in adipocytes than insulin treatment alone. We found that erythropoietin induced the trafficking of glucose transporter 4 to the plasma membrane. Our data showed that erythropoietin significantly decreased blood glucose levels both in vivo and in vitro, in part, by increasing glucose uptake via the activation of Akt pathway. Preliminary data revealed that adipocytes most likely exhibit a specific receptor for erythropoietin.

Ongoing rubella outbreak among adolescents in Salaj, Romania, September 2011-January 2012.

A rubella outbreak has been ongoing in Salaj, Romania since September 2011 involving 1,840 probable and confirmed cases among mainly unvaccinated adolescents. The index case had onset of illness on 6 September 2011. The highest number of cases was recorded among 10­14-year-olds and 15­19-year-olds. Complications were recorded for 11 cases and included meningitis and arthritis. Although the peak has passed, surveillance is being maintained in the region.

Circulatory consequences of reduced endogenous nitric oxide production during small-volume resuscitation.

Hypertonic small-volume resuscitation transiently restores the cardiovascular function during various circulatory disturbances. Nitric oxide (NO) is an important mediator of flow-induced peripheral and central hemodynamic changes, and therefore, we hypothesized that a decreased endogenous NO production could influence the consequences and the effectiveness of hypertonic fluid therapy. The main goal of this study was to outline and compare the circulatory effects small volume hypertonic saline-dextran (HSD, 7.5% NaCl-10% dextran; 4 ml/kg iv) infusion with (n=7) or without (n=7) artificially diminished NO production in normovolemic anesthetized dogs. HSD administration significantly increased cardiac index (CI), coronary flow (CF) and myocardial contractility, and elevated plasma nitrite/nitrate (NOx) and endothelin-1 (ET-1) levels. However, the late (2 h) postinfusion period was characterized by significantly decreased myocardial NO synthase (NOS) and enhanced myeloperoxidase activities. Pre-treatment with the non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) immediately increased cardiac contractility, and the HSD-induced CI and CF elevations and the positive inotropy were absent. Additionally, plasma ET-1 levels increased and NOx levels were significantly decreased. In conclusion, our results demonstrate that HSD infusion leads to preponderant vasoconstriction when endogenous NO synthesis is diminished, and this could explain the loss of effectiveness of HSD resuscitation in NO-deficient states.

Ongoing measles outbreak in Romania, 2011.

Since January 2011 Romania has been experiencing a measles outbreak with 2,072 cases notified in 29 of the 42 Romanian districts. Most cases occurred in the north-western part of the country among unvaccinated children with the highest number of cases (893 cases) registered in children aged one to four years. This report underlines once more the need for additional measures targeting susceptible populations to achieve high vaccination coverage with two doses of measles-mumps-rubella vaccine.

A chronic generalized bi-directional brain-machine interface.

A bi-directional neural interface (NI) system was designed and prototyped by incorporating a novel neural recording and processing subsystem into a commercial neural stimulator architecture. The NI system prototype leverages the system infrastructure from an existing neurostimulator to ensure reliable operation in a chronic implantation environment. In addition to providing predicate therapy capabilities, the device adds key elements to facilitate chronic research, such as four channels of electrocortigram/local field potential amplification and spectral analysis, a three-axis accelerometer, algorithm processing, event-based data logging, and wireless telemetry for data uploads and algorithm/configuration updates. The custom-integrated micropower sensor and interface circuits facilitate extended operation in a power-limited device. The prototype underwent significant verification testing to ensure reliability, and meets the requirements for a class CF instrument per IEC-60601 protocols. The ability of the device system to process and aid in classifying brain states was preclinically validated using an in vivo non-human primate model for brain control of a computer cursor (i.e. brain-machine interface or BMI). The primate BMI model was chosen for its ability to quantitatively measure signal decoding performance from brain activity that is similar in both amplitude and spectral content to other biomarkers used to detect disease states (e.g. Parkinson's disease). A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection. These techniques have the potential to be generalized beyond motor prosthesis, and are being explored for unmet needs in other neurological conditions such as movement disorders, stroke and epilepsy.