Atom lithography without laser cooling

Using direct-write atom lithography, Fe nanolines are deposited with a pitch of 186 nm, a full width at half maximum (FWHM) of 50 nm, and a height of up to 6 nm. These values are achieved by relying on geometrical collimation of the atomic beam, thus without using laser collimation techniques. This opens the way for applying direct-write atom lithography to a wide variety of elements.Comment: 7 pages, 11 figure

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging

Objectives: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. Methods: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring gamma-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. Results: Despite the low CT doses, a median increase of 0.13 gamma-H2AX foci/cell was observed. Plotting the induced gamma-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13% respectively. Conclusion: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols

Phase I study of high-dose epirubicin and vinorelbine in previously untreated non-small-cell lung cancer stage IIIB-IV.

The aim of the study was to determine the maximum tolerated dose (MTD) for the combination of high-dose epirubicin and vinorelbine in chemotherapy-naive patients with inoperable non-small-cell lung cancer (NSCLC). Twenty-one patients with stage IIIB and IV NSCLC were treated in a single-centre study with escalating doses of epirubicin and vinorelbine given on an outpatient basis. The first dose level comprised epirubicin 100 mg m-2 on day 1 and vinorelbine 20 mg m-2 (days 1 and 8) given intravenously every 3 weeks. Escalating doses for epirubicin and vinorelbine were respectively 120 (day 1) and 20 (days 1 and 8), 120 (day 1) and 25 (days 1 and 8) and 135 (day 1) and 25 (days 1 and 8) mg m-2. Inclusion criteria were age < or = 75 years, ECOG performance score < or = 2 and normal renal, hepatic and bone marrow functions. Dose-limiting toxicities were thrombocytopenia grade II and neutropenia grade III on day 8, febrile neutropenia, and neutropenia lasting > 7 days. No dose-limiting toxicity (DLT) was observed at the first dose level; at the 135/25 mg m-2 dose level three out of six patients had a DLT which was considered as unacceptable. The only non-haematological toxicity reaching grade III was nausea/vomiting. One patient showed cardiac toxicity. No neurotoxicity and no treatment-related deaths were seen. The maximum tolerated dose of epirubicin and vinorelbine is 135 mg m-2 (day 1) and 25 mg m-2 (days 1 and 8) respectively, causing mainly haematological toxicity. The recommended dose of epirubicin and vinorelbine for phase II studies is found to be 120 mg m-2 and 20 mg m-2 respectively

A Quantitative Chemicals' Mixture Risk Assessment Approach For Contaminants Of Emerging Concern Management In Drinking Water

Uncertainties on occurrence and hazard of mixtures of Contaminants of Emerging Concern (CECs) in drinking water (DW) challenge water utilities and decision makers in prioritizing these compounds in, respectively, interventions for the optimization of DW treatment and DW regulations. Continuous development of quantitative risk assessment procedures addressing adverse effects of CECs supports decision-making regarding mitigation actions in minimizing health risks. We propose a novel, quantitative chemical risk assessment (QCRA) approach for mixtures of CECs in DW. The risks are evaluated with the aid of the benchmark quotient probabilistic distribution and including uncertainties in both (i) exposure assessment using occurrence data of different DW sources and simulating DW treatment by granular activated carbon and (ii) hazard assessment steps. The QCRA was applied to compare risks deriving from the presence of alkylphenols mixtures in tap or bottled DW, and to evaluate how actual DW consumption habits affect health risks

Reliability of computerized image analysis for the evaluation of serial synovial biopsies in randomized controlled trials in rheumatoid arthritis

Analysis of biomarkers in synovial tissue is increasingly used in the evaluation of new targeted therapies for patients with rheumatoid arthritis (RA). This study determined the intrarater and inter-rater reliability of digital image analysis (DIA) of synovial biopsies from RA patients participating in clinical trials. Arthroscopic synovial biopsies were obtained before and after treatment from 19 RA patients participating in a randomized controlled trial with prednisolone. Immunohistochemistry was used to detect CD3(+ )T cells, CD38(+ )plasma cells and CD68(+ )macrophages. The mean change in positive cells per square millimetre for each marker was determined by different operators and at different times using DIA. Nonparametric tests were used to determine differences between observers and assessments, and to determine changes after treatment. The intraclass correlations (ICCs) were calculated to determine the intrarater and inter-rater reliability. Intrarater ICCs showed good reliability for measuring changes in T lymphocytes (R = 0.87), plasma cells (R = 0.62) and macrophages (R = 0.73). Analysis by Bland–Altman plots showed no systemic differences between measurements. The smallest detectable changes were calculated and their discriminatory power revealed good response in the prednisolone group compared with the placebo group. Similarly, inter-rater ICCs also revealed good reliability for measuring T lymphocytes (R = 0.68), plasma cells (R = 0.69) and macrophages (R = 0.72). All measurements identified the same cell types as changing significantly in the treated patients compared with the placebo group. The measurement of change in total positive cell numbers in synovial tissue can be determined reproducibly for various cell types by DIA in RA clinical trials

Vaginal cuff dehiscence in laparoscopic hysterectomy: influence of various suturing methods of the vaginal vault

Vaginal cuff dehiscence (VCD) is a severe adverse event and occurs more frequently after total laparoscopic hysterectomy (TLH) compared with abdominal and vaginal hysterectomy. The aim of this study is to compare the incidence of VCD after various suturing methods to close the vaginal vault. We conducted a retrospective cohort study. Patients who underwent TLH between January 2004 and May 2011 were enrolled. We compared the incidence of VCD after closure with transvaginal interrupted sutures versus laparoscopic interrupted sutures versus a laparoscopic single-layer running suture. The latter was either bidirectional barbed or a running vicryl suture with clips placed at each end commonly used in transanal endoscopic microsurgery. Three hundred thirty-one TLHs were included. In 75 (22.7 %), the vaginal vault was closed by transvaginal approach; in 90 (27.2 %), by laparoscopic interrupted sutures; and in 166 (50.2 %), by a laparoscopic running suture. Eight VCDs occurred: one (1.3 %) after transvaginal interrupted closure, three (3.3 %) after laparoscopic interrupted suturing and four (2.4 %) after a laparoscopic running suture was used (p = .707). With regard to the incidence of VCD, based on our data, neither a superiority of single-layer laparoscopic closure of the vaginal cuff with an unknotted running suture nor of the transvaginal and the laparoscopic interrupted suturing techniques could be demonstrated. We hypothesise that besides the suturing technique, other causes, such as the type and amount of coagulation used for colpotomy, may play a role in the increased risk of VCD after TLH

The Dutch secret: how to provide safe drinking water without chlorine in the Netherlands

The Netherlands is one of the few countries where chlorine is not used at all, neither for primary disinfection nor to maintain a residual disinfectant in the distribution network. The Dutch approach that allows production and distribution of drinking water without the use of chlorine while not compromising microbial safety at the tap, can be summarized as follows: &lt;br&gt; 1. Use the best source available, in order of preference:&lt;br&gt; &amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;ndash; microbiologically safe groundwater,&lt;br&gt; &amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;ndash; surface water with soil passage such as artificial recharge or bank filtration,&lt;br&gt; &amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;nbsp;&amp;ndash; direct treatment of surface water in a multiple barrier treatment;&lt;br&gt; 2. Use a preferred physical process treatment such as sedimentation, filtration and UV-disinfection. If absolutely necessary, also oxidation by means of ozone or peroxide can be used, but chlorine is avoided;&lt;br&gt; 3. Prevent ingress of contamination during distribution;&lt;br&gt; 4. Prevent microbial growth in the distribution system by production and distribution of biologically stable (biostable) water and the use of biostable materials;&lt;br&gt; 5. Monitor for timely detection of any failure of the system to prevent significant health consequences. &lt;br&gt;&lt;br&gt; New developments in safe drinking water in the Netherlands include the adaptation of the Dutch drinking water decree, implementation of quantitative microbial risk assessment (QMRA) by water companies and research into source water quality, drinking water treatment efficacy, safe distribution and biostability of drinking water during distribution and &lt;i&gt;Legionella&lt;/i&gt;. This paper summarizes how the Dutch water companies warrant the safety of the drinking water without chlorine

Deep Learning-Based Regression and Classification for Automatic Landmark Localization in Medical Images

In this study, we propose a fast and accurate method to automatically localize anatomical landmarks in medical images. We employ a global-to-local localization approach using fully convolutional neural networks (FCNNs). First, a global FCNN localizes multiple landmarks through the analysis of image patches, performing regression and classification simultaneously. In regression, displacement vectors pointing from the center of image patches towards landmark locations are determined. In classification, presence of landmarks of interest in the patch is established. Global landmark locations are obtained by averaging the predicted displacement vectors, where the contribution of each displacement vector is weighted by the posterior classification probability of the patch that it is pointing from. Subsequently, for each landmark localized with global localization, local analysis is performed. Specialized FCNNs refine the global landmark locations by analyzing local sub-images in a similar manner, i.e. by performing regression and classification simultaneously and combining the results. Evaluation was performed through localization of 8 anatomical landmarks in CCTA scans, 2 landmarks in olfactory MR scans, and 19 landmarks in cephalometric X-rays. We demonstrate that the method performs similarly to a second observer and is able to localize landmarks in a diverse set of medical images, differing in image modality, image dimensionality, and anatomical coverage.Comment: 12 pages, accepted at IEEE transactions in Medical Imagin

The Psychiatric Case Register Middle Netherlands

<p>Abstract</p> <p>Background</p> <p>The Psychiatric Case Register Middle Netherlands (PCR-MN) registers the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre of the Netherlands. In 2010 the follow-up period was over ten years. In this paper we describe the content, aims and research potential of this case register.</p> <p>Description</p> <p>All mental healthcare institutions in the middle-western part of the province of Utrecht participate in the PCR-MN case register. All in- and out-patients treated in these institutions have been included in the database from the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to in- and out-patient clinics and basic demographics are recorded. A major advantage of this register is the possibility to link patients anonymously from the PCR-MN cohort to other databases to analyze relationships with determinants and outcomes, such as somatic healthcare consumption, mortality, and demographics, which further increases the research potential</p> <p>Conclusions</p> <p>The PCR-MN database has a large potential for scientific research because of its size, duration of follow-up and ability to link with additional databases, and is accessible for academic researchers.</p

Doppler-free frequency modulation spectroscopy of atomic erbium in a hollow cathode discharge cell

The erbium atomic system is a promising candidate for an atomic Bose-Einstein condensate of atoms with a non-vanishing orbital angular momentum ($L \neq 0$) of the electronic ground state. In this paper we report on the frequency stabilization of a blue external cavity diode laser system on the 400.91 $nm$ laser cooling transition of atomic erbium. Doppler-free saturation spectroscopy is applied within a hollow cathode discharge tube to the corresponding electronic transition of several of the erbium isotopes. Using the technique of frequency modulation spectroscopy, a zero-crossing error signal is produced to lock the diode laser frequency on the atomic erbium resonance. The latter is taken as a reference laser to which a second main laser system, used for laser cooling of atomic erbium, is frequency stabilized