Reading a GEM with a VLSI pixel ASIC used as a direct charge collecting anode

In MicroPattern Gas Detectors (MPGD) when the pixel size is below 100 micron and the number of pixels is large (above 1000) it is virtually impossible to use the conventional PCB read-out approach to bring the signal charge from the individual pixel to the external electronics chain. For this reason a custom CMOS array of 2101 active pixels with 80 micron pitch, directly used as the charge collecting anode of a GEM amplifying structure, has been developed and built. Each charge collecting pad, hexagonally shaped, realized using the top metal layer of a deep submicron VLSI technology is individually connected to a full electronics chain (pre-amplifier, shaping-amplifier, sample and hold, multiplexer) which is built immediately below it by using the remaining five active layers. The GEM and the drift electrode window are assembled directly over the chip so the ASIC itself becomes the pixelized anode of a MicroPattern Gas Detector. With this approach, for the first time, gas detectors have reached the level of integration and resolution typical of solid state pixel detectors. Results from the first tests of this new read-out concept are presented. An Astronomical X-Ray Polarimetry application is also discussed.Comment: 11 pages, 14 figures, presented at the Xth Vienna Conference on Instrumentation (Vienna, February 16-21 2004). For a higher resolution paper contact [email protected]

Mendelian Randomization with Incomplete Exposure Data: a Bayesian Approach

We expand Mendelian Randomization (MR) methodology to deal with randomly missing data on either the exposure or the outcome variable, and furthermore with data from nonindependent individuals (eg components of a family). Our method rests on the Bayesian MR framework proposed by Berzuini et al (2018), which we apply in a study of multiplex Multiple Sclerosis (MS) Sardinian families to characterise the role of certain plasma proteins in MS causation. The method is robust to presence of pleiotropic effects in an unknown number of instruments, and is able to incorporate inter-individual kinship information. Introduction of missing data allows us to overcome the bias introduced by the (reverse) effect of treatment (in MS cases) on level of protein. From a substantive point of view, our study results confirm recent suspicion that an increase in circulating IL12A and STAT4 protein levels does not cause an increase in MS risk, as originally believed, suggesting that these two proteins may not be suitable drug targets for MS

A gas pixel detector for x-ray polarimetry

Even though lacking of solid experimental verifications, X-ray polarimetry is strongly established as a deep diagnostic tool for probing the emission mechanisms in astronomical sources of high energy radiation. The recent development of new, more efficient instrumentation, as well as the renewed interest of the theoreticians, has drawn a significant attention to the field. Particularly, the exploitation of the photoelectric effect for deriving polarization information seems to promise a great advance in sensitivity with respect to the conventional techniques. To this aim we have designed, produced and tested a CMOS VLSI array of 2101 pixels (with 80 μm pitch), to be directly used as the charge collecting anode of a Gas Electron Multiplier (GEM). Each pixel is fully covered by a hexagonal metal electrode and each of these electrodes is individually connected to a full electronics chain, built immediately below it; in this sense detector and read-out electronics become virtually the same thing. Even though we focus our attention on the polarimetric applications, our achievements are highly significant for the whole field of development of gas detectors, which for the first time reach the level of integration and resolution typical of solid state detectors

Incidence of Type 1 Diabetes Has Doubled in Rome and the Lazio Region in the 0- to 14-Year Age-Group: A 6-Year Prospective Study (2004-2009)

n/

Gas Pixel Detectors for X-ray Polarimetry applications

We discuss a new class of Micro Pattern Gas Detectors, the Gas Pixel Detector (GPD), in which a complete integration between the gas amplification structure and the read-out electronics has been reached. An Application-Specific Integrated Circuit (ASIC) built in deep sub-micron technology has been developed to realize a monolithic device that is, at the same time, the pixelized charge collecting electrode and the amplifying, shaping and charge measuring front-end electronics. The CMOS chip has the top metal layer patterned in a matrix of 80 micron pitch hexagonal pixels, each of them directly connected to the underneath electronics chain which has been realized in the remaining five layers of the 0.35 micron VLSI technology. Results from tests of a first prototype of such detector with 2k pixels and a full scale version with 22k pixels are presented. The application of this device for Astronomical X-Ray Polarimetry is discussed. The experimental detector response to polarized and unpolarized X-ray radiation is shown. Results from a full MonteCarlo simulation for two astronomical sources, the Crab Nebula and the Hercules X1, are also reported.Comment: 16 pages, 20 figures, accepted for publication in Nuclear Instruments and Methods in Physics Research Section

Opening a New Window to Fundamental Physics and Astrophysics: X-ray Polarimetry

An extensive theoretical literature predicts that X-ray Polarimetry can directly determine relevant physical and geometrical parameters of astrophysical sources, and discriminate between models further than allowed by spectral and timing data only. X-ray Polarimetry can also provide tests of Fundamental Physics. A high sensitivity polarimeter in the focal plane of a New Generation X-ray telescope could open this new window in the High Energy Sky.Comment: 8 pages 1 table 14 figure

Association between Protective and Deleterious HLA Alleles with Multiple Sclerosis in Central East Sardinia

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13–0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26–2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Recognising Victimhood: Lessons from the International Criminal Court and Mass Claim Programmes for the Compensation Procedure Parallel to the Trial of International Crimes in the Netherlands

In the Netherlands, the Dutch criminal court in The Hague (hereinafter: ‘Netherlands International Crimes Court’ or ‘NIC court’) is assigned to try international crimes, and to provide compensation to victims of such crimes. Whereas it has specific criminal laws at its disposal to try international crimes, it applies ‘regular’ Dutch civil law to assess claims for compensation. Yet compensation for international crimes entails challenges that are quite different from domestic crimes: international crimes are normally committed against a large number of victims, and frequently result in bodily harm. This article argues that the NIC court will most likely rule a large number of claims for compensation inadmissible, as a consequence of which victims cannot benefit from the advantages inherent in the award of compensation within the criminal process. It then explores the adjudicative and reparatory standards that the International Criminal Court and mass claim programmes have applied to simplify both the adjudication of a large number of claims, and the calculation of a large number of instances of bodily damage. It is submitted that adoption by the NIC court of international reparatory standards could facilitate the assessment of a large number of civil claims within the criminal process, without prejudice to the legitimate interests of the defendant for an adequate procedure. However, these standards require the NIC court to strike a new balance between tailor-made compensation and symbolic compensation, and thereby between corrective justice and restorative justice