A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Background: Homozygous familial hypercholesterolemia (hoFH) is a rare inherited disorder characterized by extreme elevation of low-density lipoprotein (LDL) cholesterol, accelerated coronary artery disease, and premature death. Aggressive LDL-lowering therapies are important for survival, but these are not available worldwide. Objective: The aim of the study was to compare and contrast cardiovascular outcomes and mortality of hoFH patients in 2 countries with disparate use of lipoprotein apheresis (LA) and modern therapies for lowering LDL cholesterol. Methods: A retrospective study was undertaken comparing cardiovascular disease (CVD)-free survival and mortality in 44 hoFH patients who were treated with statins but not LA, from a center in Beijing, China, and 18 hoFH patients who were treated with LA and novel therapies from an early age, from a center in Rome, Italy. Results: CVD-free survival and survival were significantly reduced in Chinese patients compared with the Italian patients after 30 years of follow-up (log-rank P <.01). In a pooled analysis, cardiovascular survival was significantly increased with earlier age at treatment, longer duration of treatment, and lower on-treatment LDL cholesterol concentrations (P <.05). In addition, the probability of a CVD event and death were increased in patients that carried a null mutation in the LDLR or had elevated lipoprotein(a). Conclusions: We show that coronary artery disease outcomes in patients with hoFH can be significantly improved with earlier and potent LDL cholesterol lowering with pharmacotherapies and LA. This has major implications for countries, such as China, where the models of care for hoFH remains underdeveloped

Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM ) can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant). Odds Ratio (OR) was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11). Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5) and autoimmune thyroiditis (p=0.02; OR=9.2). On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21) and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07). Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11). As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61), while DQ2 (p=0.03; OR=0.5) and DQ3 (p=0.002; OR= 0.5) may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5). Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients

Anomalie cromosomiche, valutate come frequenza di micronuclei spontanei, in soggetti con fenomeno di Raynaud sospetto presclerodermico [Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon]

Objective: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud’s phenomenon (RP), by means of molecular cytogenetic analysis. Methods: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed. Results: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39±15.2 vs 10±2.1 and 9.8±3.5 respectively p<0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44±8.1) as compared to subjects with different antibody pattern (26±7.1). Conclusions: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP

HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets

We conducted this study to determine the HLA class II allele associations in a large cohort of patients of homogeneous ethnic derivation with systemic lupus erythematosus (SLE). The large sample size allowed us to stratify patients according to their clinical and serologic characteristics. We studied 577 European Caucasian patients with SLE. Antinuclear antibodies (Hep-2 cells), anti-dsDNA antibodies (Crithidia luciliae), and antibodies to extractable nuclear antigens Ro (SS-A), La (SS-B), U1-RNP, Sm, Jo1, SCL70, and PCNA, were detected in all patients. Molecular typing of HLA-DRB1, DRB3, DQA1, and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We found a significantly increased frequency of DRB1*03, DRB1*15, DRB1*16, DQA1*0102, DQB1*0502, DQB1*0602, DQB1*0201, DQB1*0303, and DQB1*0304 in lupus patients as compared with healthy controls. In addition, DRB1*03 was associated with anti-Ro, anti-La, pleuritis, and involvement of lung, kidney, and central nervous system. DRB1*15 and DQB1*0602 were associated with anti-dsDNA antibodies; DQB1*0201 with anti-Ro and anti-La, leukopenia, digital skin vasculitis, and pleuritis; and DQB1*0502 was associated with anti-Ro, renal involvement, discoid lupus, and livedo reticularis. In conclusion, our study shows some new HLA clinical and serologic associations in SLE and further confirms that the role of MHC genes is mainly to predispose to particular serologic and clinical manifestations of this disease

Fabrication of a hydrogenated amorphous silicon detector in 3-d geometry and preliminary test on planar prototypes

Hydrogenated amorphous silicon (a-Si:H) can be produced by plasma-enhanced chemical vapor deposition (PECVD) of SiH4 (silane) mixed with hydrogen. The resulting material shows outstanding radiation hardness properties and can be deposited on a wide variety of substrates. Devices employing a-Si:H technologies have been used to detect many different kinds of radiation, namely, minimum ionizing particles (MIPs), X-rays, neutrons, and ions, as well as low-energy protons and alphas. However, the detection of MIPs using planar a-Si:H diodes has proven difficult due to their unsatisfactory S/N ratio arising from a combination of high leakage current, high capacitance, and limited charge collection efficiency (50% at best for a 30 µm planar diode). To overcome these limitations, the 3D-SiAm collaboration proposes employing a 3D detector geometry. The use of vertical electrodes allows for a small collection distance to be maintained while preserving a large detector thickness for charge generation. The depletion voltage in this configuration can be kept below 400 V with a consequent reduction in the leakage current. In this paper, following a detailed description of the fabrication process, the results of the tests performed on the planar p-i-n structures made with ion implantation of the dopants and with carrier selective contacts are illustrated

Testing of planar hydrogenated amorphous silicon sensors with charge selective contacts for the construction of 3D-detectors

Hydrogenated Amorphous Silicon (a-Si:H) is a well known material for its intrinsic radiation hardness and is primarily utilized in solar cells as well as for particle detection and dosimetry. Planar p-i-n diode detectors are fabricated entirely by means of intrinsic and doped PECVD of a mixture of Silane (SiH4) and molecular hydrogen. In order to develop 3D detector geometries using a-Si:H, two options for the junction fabrication have been considered: ion implantation and charge selective contacts through atomic layer deposition. In order to test the functionality of the charge selective contact electrodes, planar detectors have been fabricated utilizing this technique. In this paper, we provide a general overview of the 3D fabrication project followed by the results of leakage current measurements and X-ray dosimetric tests performed on planar diodes containing charge selective contacts to investigate the feasibility of the charge selective contact methodology for integration with the proposed 3D detector architectures

Progress in Diamond Detector Development

Detectors based on Chemical Vapor Deposition (CVD) diamond have been used successfully in Luminosity and Beam Condition Monitors (BCM) in the highest radiation areas of the LHC. Future experiments at CERN will accumulate an order of magnitude larger fluence. As a result, an enormous effort is underway to identify detector materials that can operate under fluences of 1 · 1016 n cm−2 and 1 · 1017 n cm−2. Diamond is one candidate due to its large displacement energy that enhances its radiation tolerance. Over the last 30 years the RD42 collaboration has constructed diamond detectors in CVD diamond with a planar geometry and with a 3D geometry to extend the material's radiation tolerance. The 3D cells in these detectors have a size of 50 µm×50 µm with columns of 2.6 µm in diameter and 100 µm×150 µm with columns of 4.6 µm in diameter. Here we present the latest beam test results from planar and 3D diamond pixel detectors