Performance of a spaghetti calorimeter prototype with tungsten absorber and garnet crystal fibres

A spaghetti calorimeter (SPACAL) prototype with scintillating crystal fibres was assembled and tested with electron beams of energy from 1 to 5 GeV. The prototype comprised radiation-hard Cerium-doped GdAlGaO (GAGG:Ce) and YAlO (YAG:Ce) embedded in a pure tungsten absorber. The energy resolution was studied as a function of the incidence angle of the beam and found to be of the order of 10%/E⊕1%, in line with the LHCb Shashlik technology. The time resolution was measured with metal channel dynode photomultipliers placed in contact with the fibres or coupled via a light guide, additionally testing an optical tape to glue the components. Time resolution of a few tens of picosecond was achieved for all the energies reaching down to (18.5 ± 0.2) ps at 5 GeV.We acknowledge support by the CERN Strategic Programme on Technologies for Future Experiments, https://ep-rnd.web.cern.ch/, by the MCIN/AEI, GenCat and GVA (Spain), and by the NSFC (China) under grant Nos. 12175005, 12061141007. The measurements were performed at the Test Beam Facility at DESY Hamburg (Germany), a member of the Helmholtz Association (HGF). The authors would like to thank T. Schneider, H. Gerwig, N. Siegrist, and D. Deyrail (CERN) for their help in designing and assembling the prototype and the set-up, A. Barnyakov, Budker Institute of Nuclear Physics (BINP), Novosibirsk, for kindly providing the MCPs, and the ITEP ATLAS group for the DWCs

Prognostic value of donor cytotoxic T-lymphocyte precursor frequencies for acute graft-versus-host disease in hematopoietic stem cell transplantation from HLA-matched siblings: A single center experience in a cohort of 92 patients

We investigated the prognostic value of cytotoxic T-lymphocyte precursor frequencies (CTL-p-f) for the development of graft-versus-host disease (GvHD) in a cohort of 92 recipients of a hematopoietic stem cell transplantation from HLA-matched sibling donors. CTL-p-f and clinical variables were correlated with acute GvHD and chronic GvHD in univariate and multivariate analyses. CTL-p-f resulted an independent risk factor for severe acute GvHD. Moreover, a trend towards a correlation between CTL-p-f and chronic GvHD was observed. In summary CTL-p-f may be considered as a functional assay useful for identifying patients at high risk of severe GVHD. ©2006 Ferrata Storti Foundation

Obstructed defecation syndrome associated with paradoxical puborectalis contraction: osteopathic treatment versus anal biofeedback. Results of a pilot study

Background: Biofeedback is the most widespread rehabilitative therapy for the treatment of anismus after failed conservative treatment. Osteopathy represents an alternative therapy for constipation. The aim of this study was to evaluate short- and long-term results of osteopathic treatment as compared to biofeedback in patients with dyssynergic defecation. Methods: This was a prospective cohort pilot study on 30 patients with dyssynergic defecation enrolled at the Colorectal Clinic of the University Hospital of Ferrara, Italy, from May 2015 to May 2016 and followed until May 2020. Dyssynergic defecation was defined as the inappropriate contraction of the pelvic floor or less than 20% relaxation of basal resting sphincter pressure (on anal manometry) with adequate propulsive forces during attempted defecation. Dyssynergic patients were divide into 2 treatment groups: 15 patients had osteopathy and 15 patients had biofeedback. Before and 3 months after rehabilitation treatment, all patients had anorectal manometry, defecography, and ultrasound, and were evaluated with the Cleveland Clinic Florida (CCF) constipation score, obstructed defecation syndrome (ODS) score, Colo-rectal-anal Distress Inventory (CRADI-8), Colo-rectal-anal Impact Questionnaire (CRAIQ-7), and the Brusciano Score (BS). To evaluate the efficacy of osteopathy and biofeedback in the long-term, all patients completed the above-mentioned questionnaires 5 years later via a telephone interview. Results: The two treatments were similarly effective in the short term with reduction in questionnaires scores, and increase in the percentage of anal sphincter release at straining at anorectal manometry in both groups. The ODS score was significantly reduced in biofeedback group (p = 0.021). The 3-month post-treatment BS was lower in the osteopathy group, but this just failed to reach statistical significance (p = 0.050). Periodic rehabilitation reinforcements were provided. The CCF constipation score decreased significantly in the osteopathy group (p = 0.023) after 5 years. Conclusions: Osteopathy is a promising treatment for dyssynergic defecation, and it can be associated with biofeedback

Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings

The measurement of precursor frequencies of donor anti-recipient cytotoxic T lymphocytes (CTL-p) has been shown to predict the incidence and the severity of acute graft-versus-host disease (aGVHD) in unrelated donor bone marrow transplantation (BMT). In HLA-identical sibling BMT, where aGVHD is most likely caused by minor histocompatibility antigen mismatches, this assay did not appear to be sensitive enough to provide similar predictive information. In this study, the CTL-p frequencies and the incidence and severity of aGVHD in 51 onco-hematological patients transplanted from HLA-identical siblings were compared. Sibling donors were selected on the basis of HLA identity using serological typing for HLA-A, B, C antigens, whereas HLA-DRB was tested by molecular analysis. Sibling identity was also confirmed by DNA heteroduplex analyses. Fifteen out of 21 (71%) patients with high precursor frequency (>1:100 x 103) and 12 out of 30 (40%) with low precursor frequency (<1:100 x 103) experienced clinically significant (II-IV) aGVHD. A significant correlation (P = 0.04) between CTL-p frequency and severe aGVHD was demonstrated. Moreover there was a positive trend for a high frequency response according to an increasing grade of aGVHD, which was statistically significant (P = 0.04). In our experience the CTL-p assay is a helpful predictive test for aGVHD in HLA-identical sibling BMT, indicating high risk patients possibly requiring additional prophylaxis

Significance of CTLA-4 and CD14 genetic polymorphisms in clinical outcome after allogeneic stem cell transplantation [3]

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Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; \u3c72 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (\u3c72 for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage

Interaction between gene polymorphisms of nitric oxide synthase and renin-angiotensin system in the progression of membranous glomerulonephritis.

Background. The renin\u2013angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty. Methods. The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/ deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy and followup 5 years (Kaplan\u2013Meier and Cox multivariate analysis). The control group consisted of DNA from 171 organ donors. Results. We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (2\ubc 4.80, P\ubc0.028; HR\ubc1.97, 95% CI 0.98\u20133.96) and the allele T of AGT (M235T) (2\ubc5.09, P\ubc0.024; HR\ubc2.84, 95%RESULTS: We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of the single gene variations. CONCLUSION: This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes

Role of non-HLA genetic polymorphisms in graft-versus-host disease after haematopoietic stem cell transplantation

Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD. © 2006 The Authors

A comparison of cytotoxic T lymphocyte precursor frequencies in responder/stimulator pairs with increasing degrees of mismatch

Limiting dilution assays of helper or cytotoxic T cell precursor (HTL-p and CTL-p) frequencies have been developed to measure, with high sensitivity and specificity, donor/recipient alloreactivity before bone marrow transplantation (BMT). Most studies demonstrated a significant correlation between the frequency of donor host-specific CTL-p before transplant and the incidence of severe (≥ grade II) acute graft-versus-host disease (aGvHD) in unrelated donor BMT. Recently we demonstrated that the CTL-p assay was sensitive enough to provide similar predictive information also in HLA-identical sibling BMT. In the present study, the CTL-p frequencies were compared in four groups of responder/stimulator pairs with different degree of mismatch: (1) monozygotic twins (MZ) (n=7), (2) HLA-identical sibling pairs (SIB) (n=67), (3) HLA-matched unrelated pairs (HLA-A, B serologically and HLA-DRBI allele-matched) (MUP) (n=59), (4) 2-4 antigen HLA-mismatched pairs (MM) (n=27). Logistic regression analysis showed that as mismatch increased, the probability of a high (&gt;1:100.000) CTL-p frequency (HF) significantly increased. Then, MUP group was divided in two subgroups: (3a) well-matched pairs (WM) (n=20): matched for HLA-DRB3, B4, B5 alleles and, by DNA heteroduplex analysis, for HLA-A, B genes; (3b) matched pairs (M) (n=39): with either a single HLA-A, B mismatch as revealed by DNA heteroduplex analysis, or a single mismatch in HLA-DRB3, B4, B5 alleles. The CTL-p frequencies were analysed again in the five groups, re-using a logistic regression model. The probability of a HF response was significantly higher in the M than in SIB group. Otherwise, WM and SIB groups had the same probability of a HF response. The probability of a HF response in the M group was significantly higher than in WM group, and lower, though not significantly, than in MM group. The results confirmed not only the power of CTL-p assay in the identification of functionally significant polymorphisms, but also in measuring the degree of mismatch in responder/stimulator pairs. They also showed that when unrelated pairs were more closely matched, CTL-p frequencies approached those of SIB. In conclusion, the CTL-p assay may be an important "in vitro" tool in BMT helping also to predict alloreactivity due to minor histocompatibility antigen differences, which still remain difficult to define despite the improvements in unrelated donor matching. © 2001 Blackwell Science Ltd,