Wafer scale manufacturing of high precision micro-optical components through X-ray lithography yielding 1800 Gray Levels in a fingertip sized chip.

We present a novel x-ray lithography based micromanufacturing methodology that offers scalable manufacturing of high precision optical components. It is accomplished through simultaneous usage of multiple stencil masks made moveable with respect to one another through custom made micromotion stages. The range of spectral flux reaching the sample surface at the LiMiNT micro/nanomanufacturing facility of Singapore Synchrotron Light Source (SSLS) is about 2 keV to 10 keV, offering substantial photon energy to carry out deep x-ray lithography. In this energy range, x-rays penetrate through resist materials with only little scattering. The highly collimated rectangular beam architecture of the x-ray source enables a full 4″ wafer scale fabrication. Precise control of dose deposited offers determined chain scission in the polymer to required depth enabling 1800 discrete gray levels in a chip of area 20 mm2 and with more than 2000 within our reach. Due to its parallel processing capability, our methodology serves as a promising candidate to fabricate micro/nano components of optical quality on a large scale to cater for industrial requirements. Usage of these fine components in analytical devices such as spectrometers and multispectral imagers transforms their architecture and shrinks their size to pocket dimension. It also reduces their complexity and increases affordability while also expanding their application areas. Consequently, equipment based on these devices is made available and affordable for consumers and businesses expanding the horizon of analytical applications. Mass manufacturing is especially vital when these devices are to be sold in large quantities especially as components for original equipment manufacturers (OEM), which has also been demonstrated through our work. Furthermore, we also substantially improve the quality of the micro-components fabricated, 3D architecture generated, throughput, capability and availability for industrial application. Manufacturing 1800 Gray levels or more through other competing techniques is either limited due to multiple process steps involved or due to unacceptably long time required owing to their pencil beam architecture. Our manufacturing technique presented here overcomes both these shortcomings in terms of the maximum number of gray levels that can be generated, and the time required to generate the same.

Pompe disease in Austria: clinical, genetic and epidemiological aspects.

In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. We found 25 patients in 24 families, 4 IOPD and 21 LOPD with a resulting prevalence of 1:350,914. The most frequent clinical manifestation in LOPD was a lower limb-girdle phenotype combined with axial weakness. Three patients were clinically pauci- or asymptomatic and were diagnosed because of persistent hyperCKemia. Diagnostic delay in LOPD was 7.4 ± 9.7 years. The most common mutation was c.-32-13T > G. All IOPD and 17 symptomatic LOPD patients are receiving ERT. Standardized follow-up was only available in six LOPD patients for the 6-min walk test (6minWT) and in ten for the forced vital capacity (FVC). Mean FVC did not decline (before ERT; 63.6 ± 39.7%; last evaluation during ERT: 61.9 ± 26.9%; P = 0.5) while there was a trend to decline in the mean distance covered by the 6minWT (before ERT: 373.5 ± 117.9 m; last evaluation during ERT: 308.5 ± 120.8 m; P = 0.077). The study shows a lower prevalence of Pompe disease in Austria than in other European countries and corroborates a limb-girdle phenotype with axial weakness as the most common clinical presentation, although asymptomatic hyperCKemia may be the first indication of LOPD.

An empirical analysis of consumers' attitudes toward pharmacies' advertising.

This study investigates current attitudes and opinions toward pharmacies' advertising. The purposes of this study were to determine (a) consumers' attitudes toward advertising by pharmacies and (b) whether age, race, income, marital status, occupation, education, sex, and number of children in household of the consumer accounted for any significant difference in attitudes toward pharmacies that advertise. The intent was to discover information that would be useful to pharmacies in planning marketing strategies and improving the quality of their advertising. The study seems to confirm the belief of many pharmacies that advertising and marketing clearly have a place in the future of pharmacists' services.

An empirical analysis of ethical and professional issues in physicians' advertising: A comparative cross-sectional study.

The purpose of this study is to investigate current attitudes and opinions of physicians' advertising and to compare them to the attitudes expressed 10 years previously. This study was designed to determine (a) consumers' attitudes toward advertising by physicians, and (b) whether age, occupation, income, education, or sex of consumer accounted for any significant difference in attitudes toward physicians who advertise. The study seems to confirm the belief of many marketing professionals that advertising and marketing do not have a place in the management and operation of professional services.

A quick technique to improve the geometry characterisation of aged HPGe detectors for MC code efficiency calculation.

During the EMRP JRP MetroMETAL project a detector image of an aged HPGe gamma-ray detector was created for MC efficiency calculation. Using the nominal construction parameters of the detector, the simulation showed unacceptably high deviations from the assured activity values. This paper describes an optimisation of a virtual detector to obtain better results using limited resources and offers comparisons of efficiency values of point and voluminous sources calculated by LABSOCS® and PENELOPE 2011.

Anomalous spectral features of a neutral bilayer graphene.

Graphene and its bilayer are two-dimensional systems predicted to show exciting many-body effects near the neutrality point. The ideal tool to investigate spectrum reconstruction effects is angle-resolved photoemission spectroscopy (ARPES) as it probes directly the band structure with information about both energy and momentum. Here we reveal, by studying undoped exfoliated bilayer graphene with ARPES, two essential aspects of its many-body physics: the electron-phonon scattering rate has an anisotropic k-dependence and the type of electronic liquid is non-Fermi liquid. The latter behavior is evident from an observed electron-electron scattering rate that scales linearly with energy from 100 meV to 600 meV and that is associated with the proximity of bilayer graphene to a two-dimensional quantum critical point of competing orders.

Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats.

We used the cheek model of itch and pain in rats to determine the dose-response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior. We also determined the dose-related effects of intracisternally injected morphine on scratching, effects that were greatly reduced by administration of the opiate antagonist naloxone. We then examined the interactions of intradermal injection of serotonin and intracisternal injection of morphine on scratching and found that the two procedures act synergistically to increase itch. These results suggest that morphine applied to the CNS is capable of producing itch and greatly increasing itch originating in the skin (hyperknesis).

An empirical analysis of the public's attitudes toward advertising hospital services: a comparative cross-sectional study.

This study investigates current opinions about hospital advertising and compares them to the attitudes expressed 25 years ago. It replicates a survey done in 1985, using the same questionnaire and population to compare responses longitudinally. The study indicates some changes in the public's opinions of hospital advertising. Although the image of hospitals remains positive, most of the 2010 respondents' opinions were rather mixed regarding whether it is proper for hospitals to advertise. The study also confirmed that the quality of service and reputation of hospitals remain more important to the public than price.

Multichannel Fourier-transform interferometry for fast signals.

Multichannel Fourier transform interferometry to measure the spectrum of arbitrarily short pulses and of fast time-varying signals was achieved using a micro/nanomanufactured multimirror array. We describe the performance of a demonstrator FTIR that works in the mid-infrared (MIR) range of 700-1400 cm(-1) and reaches a spectral resolution of 10 cm(-1) taking into account apodization. Spectral measurements down to pulse lengths of 319 µs were carried out using a mechanical camera shutter. Arbitrarily short pulses are expected feasible provided the source can deliver enough photons to overcome the noise equivalent number of photons.

Radiation-induced melting in coherent X-ray diffractive imaging at the nanoscale.

Coherent X-ray diffraction techniques play an increasingly significant role in the imaging of nanoscale structures, ranging from metallic and semiconductor to biological objects. In material science, X-rays are usually considered to be of a low-destructive nature, but under certain conditions they can cause significant radiation damage and heat loading on the samples. The qualitative literature data concerning the tolerance of nanostructured samples to synchrotron radiation in coherent diffraction imaging experiments are scarce. In this work the experimental evidence of a complete destruction of polymer and gold nanosamples by the synchrotron beam is reported in the case of imaging at 1-10 nm spatial resolution. Numerical simulations based on a heat-transfer model demonstrate the high sensitivity of temperature distribution in samples to macroscopic experimental parameters such as the conduction properties of materials, radiation heat transfer and convection. However, for realistic experimental conditions the calculated rates of temperature rise alone cannot explain the melting transitions observed in the nanosamples. Comparison of these results with the literature data allows a specific scenario of the sample destruction in each particular case to be presented, and a strategy for damage reduction to be proposed.

Multivariate analysis techniques in the forensics investigation of the postblast residues by means of Fourier transform-infrared spectroscopy.

Fourier transform-infrared (FT-IR) spectroscopy has gained considerable attention among the forensic scientists because it shows high sensitivity and selectivity and offers near real time detection of analyzed samples. However, the amount of obtained information due to complexity of the measured spectra forces the use of additional data processing. Application of the multivariate statistical techniques for the analysis of the FT-IR data seems to be necessary in order to enable feature extraction, proper evaluation, and identification of obtained spectra. In this article, an attempt to develop a feasible procedure for characterization of spectroscopic signatures of the explosive materials in the remnants after explosion has been made. All spectra were derived after analysis of samples from debris after especially prepared and performed blasts with the use of three various highly explosive materials: C-4, 2,4,6-trinitrotoluene (TNT), and pentaerythritol tetranitrate (PETN). Two well-known multivariate statistical methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA), were tested in order to classify the samples into separate classes using a broad wavelength data range (4000-600 cm(-1)) on collected spectra sets. After many trials it seems that PCA is the best choice for the mentioned earlier tasks. It was found that only three principal components carry over 99.6% of variance within the sample set. The results show that FT-IR spectroscopy in combination with multivariate methods is well-suited for identification and differentiation purposes even in quite large data sets, and for that reason forensic laboratories could employ these methods for rapid screening analysis.

Ecotoxicological characterisation of 12 incineration ashes using 6 laboratory tests.

In the European Waste List (2000/532/EC as amended) the ash of municipal waste incineration is defined as a so called mirror entry. This waste can be classified as hazardous or non-hazardous depending on the content of hazardous substances and other risk properties. For the assignment of waste in mirror entries, 14 criteria are defined. One of the criteria is H14 "ecotoxic". In the presented study, the ecotoxicological potential of 12 ashes from different incineration plants has been assessed using biological test systems. The test battery included aquatic tests with eluates (algae, daphnids, and luminescent bacteria) and terrestrial tests with solid waste (plants, earthworms and bacteria). The test results revealed a clear ecotoxicological hazard potential for some of the MWI ashes. Despite the fact that fresh ashes were several times more toxic than aged ashes both groups did not differ consistently in terms of toxicity. The results show also that there is no correlation between the biological effects and the analyzed chemical compounds of the ash samples.

A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts.

Zellweger spectrum disorders (ZSD) are diagnosed by biochemical assay in blood, urine and cultured fibroblasts and PEX gene mutation identification. In most cases studies in fibroblasts corroborate results obtained in body fluids. In 1996 Clayton and colleagues described a 10-year old girl with evidence of a peroxisome disorder, based on elevated bile acid metabolites and phytanate. At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect. Studies in our laboratory showed that she also had elevated plasma pipecolate, supporting the former diagnosis. Despite the abnormal metabolites detected in blood (phytanate, bile acid intermediates and pipecolate), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results. In addition, she had a milder clinical phenotype than usually associated with ZSD. Since complementation analysis to determine the gene defect was not possible, we screened this patient following the PEX Gene Screen algorithm (PGS). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis. Two mutations in PEX10 were identified, a frameshift mutation inherited from her father and a de novo missense mutation in a conserved functional domain on the other allele. This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum. Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver.

All-metal self-supported THz metamaterial--the meta-foil.

Modern metamaterials face functional constraints as they are commonly embedded in or deposited on dielectric materials. We provide a new solution by microfabricating a completely free-standing all-metal self-supported metamaterial. Using upright S-string architecture with the distinctive feature of metallic transverse interconnects, we form a locally stiff, globally flexible space-grid. Infrared Fourier transform interferometry reveals the typical double-peak structure of a magnetically excited left-handed and an electrically excited right-handed pass-band that is maintained under strong bending and heating, and is sensitive to dielectrics. Exploiting UV/X-ray lithography and ultimately plastic moulding, meta-foils can be mass manufactured cost-effectively to serve as optical elements.

An empirical analysis of consumers' attitudes toward physicians' advertising.

Advertising by physicians is a relatively recent phenomenon. Historically, most professions prohibited licensed members from engaging in speech activities that proposed a commercial transaction-advertising. However the history of a physician's legal right to advertise is not the main focus of this article. A brief review of the past, present, and possible future of such rights might assist readers in understanding the revolutionary constitutional and commercial speech changes that have occurred over the past three decades. A physician's legal right to advertise has developed as part of the evolutionary interpretation of the First Amendment of the U.S. Constitution. The purposes of this study were to determine (a) consumers' attitudes toward advertising by physicians and (b) whether city of residence, occupation, age, sex, race, marital status, number of children in household, total family household income, and education of the consumer accounted for any significant difference in attitude toward physicians who advertise. The intent was to discover information that would be useful to physicians in planning marketing strategies and improving the quality of their advertising. The study seems to confirm the belief of many marketing professionals that advertising and marketing clearly have a place in the future of health care services.

Free-standing THz electromagnetic metamaterials.

Using micromanufactured S-shaped gold strings suspended in free space by means of window-frames, we experimentally demonstrate an electromagnetic meta-material (EM(3)) in which the metallic structures are no longer embedded in matrices or deposited on substrates such that the response is solely determined by the geometrical parameters and the properties of the metal. Two carefully aligned and assembled window-frames form a bi-layer chip that exhibits 2D left-handed pass-bands corresponding to two different magnetic resonant loops in the range of 1.4 to 2.2 THz as characterized by Fourier transform interferometry and numerical simulation. Chips have a comparably large useful area of 56 mm(2). Our results are a step towards providing EM(3) that fulfill the common notions of a material.

Phenotype of adult Refsum disease due to a defect in peroxin 7.

The biochemical hallmark of adult Refsum disease (ARD) is an isolated deficiency in the breakdown of phytanic acid. This usually results from a PHYH gene defect, although some cases have been found to carry a PEX7 defect. We describe the phenotype of such a patient, indistinguishable from that of classic ARD. Hence, we propose the subdivision of ARD into type 1 and type 2, depending on which gene is defective.

A longitudinal assessment of consumers' attitudes toward physicians' advertising.

The purpose of this study is to investigate current attitudes and opinions toward physicians' advertising and to compare them to the attitudes expressed 20 years ago. It replicates a survey done in 1986 and uses the same questionnaire and the same population to compare responses longitudinally. Both the 1986 and 2006 respondents agreed that the public would be provided useful information through advertising by physicians, and both groups also believed that it is proper for physicians to advertise. The study seems to confirm the belief of many marketing professionals that advertising and marketing clearly have a place in the future of health care services.

Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.

BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy.

Auditory brainstem response findings and peripheral auditory sensitivity in adrenoleukodystrophy.

Measurements of the auditory brainstem response (ABR) were obtained in 96 individuals with X-linked adrenoleukodystrophy (X-ALD). The patients were divided into five diagnostic groups on the basis of neurologic diagnosis. The five groups were cerebral childhood and adolescent, pure adrenomyeloneuropathy (pure AMN), adrenomyeloneuropathy cerebral (AMN cerebral), Addison's only and symptomatic female heterozygotes. Results indicated the presence of marked ABR abnormalities for all groups most frequently involving Wave V, followed by Wave III and Wave I. Abnormalities of all interpeak latency intervals (i.e., I-III, III-V and I-V) were observed for all groups. ABR abnormalities were most frequently seen in the AMN-cerebral and pure AMN groups but were also common in the symptomatic female heterozygote group. The ABRs in the cerebral childhood and adolescent group were the least impaired of the five groups examined. Age was found to be a significant independent predictor of bilateral ABR abnormalities but VLCFA levels, MRI Loes score, and duration of symptoms were not found to be independent predictors of bilateral ABR abnormalities after adjusting for ALD phenotype. Patients with AMN were significantly more likely to have bilateral ABR abnormalities than the cerebral childhood and adolescent group after adjusting for age, duration of symptoms, EDSS score, VLCFA levels and MRI Loes scores. The prevalence of peripheral hearing loss was not found to exceed that present in age and sex matched normal control groups derived from the NHANES (1999-2000), indicating a lack of association between peripheral hearing loss and X-linked adrenoleukodystrophy. It was concluded that: (1) auditory sensitivity in X-ALD is not significantly impaired; (2) ABR abnormalities are a frequent finding and may be caused by abnormalities of fiber tracts in the region of the lateral lemniscus and inferior colliculus; and, (3) the abnormalities progress slowly and appear to be associated mainly with the AMN phenotype.