OPTIma:a tracking solution for proton computed tomography in high proton flux environments

Currently there is a large discrepancy between the currents that are used for treatments in proton beam therapy facilities and the ultra low beam currents required for many proton CT imaging systems. Here we provide details of the OPTIma silicon strip based tracking system, which has been designed for performing proton CT imaging in conditions closer to the high proton flux environments of modern spot scanning treatment facilities. Details on the physical design, sensor testing, modelling, and track reconstruction are provided along with Monte-Carlo simulation studies of the expected performance for proton beam currents of up to 50 pA at the nozzle when using a σ = ∼10 mm spot scanning cyclotron system. Using a detailed simulation of the proposed OPTIma system, a discrepancy of less than 1% on the Relative Stopping Power is found for various tissues when embedded within a 150 mm diameter Perspex sphere. It is found that by accepting up to 7 protons per bunch it is possible to operate at cyclotron beam currents up to 5 times higher than would be possible with a single proton based readout, significantly reducing the total beam time required to produce an image, while also reducing the discrepancy between the beam currents required for treatment and those used for proton CT

Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

BACKGROUND: Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters) of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I) with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. METHODS: Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI) for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250). Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. RESULTS: Three of five microsatellite markers (BAT-25, BAT-26 and D5S346) presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H). We identified in the HNPCC family a novel germline missense (c.1864C>A) mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr) amino acid substitution. CONCLUSION: This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD) and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Database this is the first report of this mutation

Embedded pitch adapters: a high-yield interconnection solution for strip sensors

A proposal to fabricate large area strip sensors with integrated, or embedded, pitch adapters is presented for the End-cap part of the Inner Tracker in the ATLAS experiment. To implement the embedded pitch adapters, a second metal layer is used in the sensor fabrication, for signal routing to the ASICs. Sensors with different embedded pitch adapters have been fabricated in order to optimize the design and technology. Inter-strip capacitance, noise, pick-up, cross-talk, signal efficiency, and fabrication yield have been taken into account in their design and fabrication. Inter-strip capacitance tests taking into account all channel neighbors reveal the important differences between the various designs considered. These tests have been correlated with noise figures obtained in full assembled modules, showing that the tests performed on the bare sensors are a valid tool to estimate the final noise in the full module. The full modules have been subjected to test beam experiments in order to evaluate the incidence of cross-talk, pick-up, and signal loss. The detailed analysis shows no indication of cross-talk or pick-up as no additional hits can be observed in any channel not being hit by the beam above 170 mV threshold, and the signal in those channels is always below 1% of the signal recorded in the channel being hit, above 100 mV threshold. First results on irradiated mini-sensors with embedded pitch adapters do not show any change in the interstrip capacitance measurements with only the first neighbors connected

Charge collection and field profile studies of heavily irradiated strip sensors for the ATLAS inner tracker upgrade

The ATLAS group has evaluated the charge collection in silicon microstrip sensors irradiated up to a fluence of 1×1016 neq/cm2, exceeding the maximum of 1.6×1015 neq/cm2 expected for the strip tracker during the high luminosity LHC (HL-LHC) period including a safety factor of 2. The ATLAS12, n+-on-p type sensor, which is fabricated by Hamamatsu Photonics (HPK) on float zone (FZ) substrates, is the latest barrel sensor prototype. The charge collection from the irradiated 1×1 cm2 barrel test sensors has been evaluated systematically using penetrating β-rays and an Alibava readout system. The data obtained at different measurement sites are compared with each other and with the results obtained from the previous ATLAS07 design. The results are very consistent, in particular, when the deposit charge is normalized by the sensor's active thickness derived from the edge transient current technique (edge-TCT) measurements. The measurements obtained using β-rays are verified to be consistent with the measurements using an electron beam. The edge-TCT is also effective for evaluating the field profiles across the depth. The differences between the irradiated ATLAS07 and ATLAS12 samples have been examined along with the differences among the samples irradiated with different radiation sources: neutrons, protons, and pions. The studies of the bulk properties of the devices show that the devices can yield a sufficiently large signal for the expected fluence range in the HL-LHC, thereby acting as precision tracking sensors

Study of surface properties of ATLAS12 strip sensors and their radiation resistance

A radiation hard nþ-in-p micro-strip sensor for the use in the Upgrade of the strip tracker of the ATLAS experiment at the High Luminosity Large Hadron Collider (HL-LHC) has been developed by the “ATLAS ITk Strip Sensor collaboration” and produced by Hamamatsu Photonics. Surface properties of different types of end-cap and barrel miniature sensors of the latest sensor design ATLAS12 have been studied before and after irradiation. The tested barrel sensors vary in “punchthrough protection” (PTP) structure, and the end-cap sensors, whose stereo-strips differ in fan geometry, in strip pitch and in edge strip ganging options. Sensors have been irradiated with proton fluences of up to 1 1016 neq/cm2 , by reactor neutron fluence of 1 1015 neq/cm2 and by gamma rays from 60Co up to dose of 1 MGy. The main goal of the present study is to characterize the leakage current for microdischarge breakdown voltage estimation, the inter-strip resistance and capacitance, the bias resistance and the effectiveness of PTP structures as a function of bias voltage and fluence. It has been verified that the ATLAS12 sensors have high breakdown voltage well above the operational voltage which implies that different geometries of sensors do not influence their stability. The inter-strip isolation is a strong function of irradiation fluence, however the sensor performance is acceptable in the expected range for HL-LHC. New gated PTP structure exhibits low PTP onset voltage and sharp cut-off of effective resistance even at the highest tested radiation fluence. The inter-strip capacitance complies with the technical specification required before irradiation and no radiation-induced degradation was observed. A summary of ATLAS12 sensors tests is presented including a comparison of results from different irradiation sites. The measured characteristics are compared with the previous prototype of the sensor design, ATLAS07

Citizenship Norms in Eastern Europe

Research on Eastern Europe stresses the weakness of its civil society and the lack of political and social involvement, neglecting the question: What do people themselves think it means to be a good citizen? This study looks at citizens’ definitions of good citizenship in Poland, Slovenia, the Czech Republic and Hungary, using 2002 European Social Survey data. We investigate mean levels of civic mindedness in these countries and perform regression analyses to investigate whether factors traditionally associated with civic and political participation are also correlated with citizenship norms across Eastern Europe. We show that mean levels of civic mindedness differ significantly across the four Eastern European countries. We find some support for theories on civic and political participation when explaining norms of citizenship, but also demonstrate that individual-level characteristics are differently related to citizenship norms across the countries of our study. Hence, our findings show that Eastern Europe is not a monolithic and homogeneous bloc, underscoring the importance of taking the specificities of countries into account

Evaluation of the performance of irradiated silicon strip sensors for the forward detector of the ATLAS Inner Tracker Upgrade

The upgrade to the High-Luminosity LHC foreseen in about ten years represents a great challenge for the ATLAS inner tracker and the silicon strip sensors in the forward region. Several strip sensor designs were developed by the ATLAS collaboration and fabricated by Hamamatsu in order to maintain enough performance in terms of charge collection efficiency and its uniformity throughout the active region. Of particular attention, in the case of a stereo-strip sensor, is the area near the sensor edge where shorter strips were ganged to the complete ones. In this work the electrical and charge collection test results on irradiated miniature sensors with forward geometry are presented. Results from charge collection efficiency measurements show that at the maximum expected fluence, the collected charge is roughly halved with respect to the one obtained prior to irradiation. Laser measurements show a good signal uniformity over the sensor. Ganged strips have a similar efficiency as standard strips

Cancer effects of formaldehyde: a proposal for an indoor air guideline value

Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings