The solid state photomultiplier: Status of photon counting beyond the near-infrared

Rockwell International's Solid State Photomultiplier (SSPM) is an impurity-band avalanche device which can count individual photons with wavelengths between 0.4 and 28 micrometers. Its response to a photon is a pulse of between 10(exp 4) and 10(exp 5) conduction electrons, making it an important device for use in phenomenology. The characteristics of the SSPM make it a potentially important device for use in astronomical applications. Contract NAS2-12400 was initiated in June 1986 to conduct modeling and characterization studies of the SSPM to provide a basis for assessing its use in astronomical systems. Some SSPM models and results of measurements which characterize the group of SSPMs recently fabricated on this contract are discussed

Time Resolution and Linearity Measurements for a Scintillating Fiber Detector Instrumented with VLPC's

The time resolution for a charged particle detection is reported for a typical scintillating fiber detector instrumented with Rockwell HISTE-IV Visible Light Photon Counters. The resolution measurements are shown to agree with a simple Monte Carlo model, and the model is used to make recomendations for improved performance. In addition, the gain linearity of a sample of VLPC devices was measured. The gain is shown to be linear for incident light intensities which produce up to approximately 600 photoelectrons per event.Comment: 18 pages, 14 figures; Submitted to Nucl. Instr & Meth. in Phys. Res. A; Please direct correspondence to [email protected]

Improved Si:As BIBIB (Back-Illuminated Blocked-Impurity-Band) hybrid arrays

Results of a program to increase the short wavelength (less than 10 microns) detective quantum efficiency, eta/beta, of Si:As Impurity Band Conduction arrays are presented. The arrays are epitaxially grown Back-Illuminated Blocked (BIB) Impurity-Band (BIBIB) 10x50 detectors bonded to switched-FET multiplexers. It is shown that the 4.7 microns detective quantum efficiency increases proportionately with the thickness of the infrared active layer. A BIB array with a thick active layer, designed for low dark current, exhibits eta/beta = 7 to 9 percent at 4.7 microns for applied bias voltages between 3 and 5 V. The product of quantum efficiency and photoelectric gain, etaG, increases from 0.3 to 2.5 as the voltage increases from 3 to 5 V. Over this voltage range, the dark current increases from 8 to 120 e(-)s(-1) at a device temperature of 4.2 K and is under 70 e(-)s(-1) for all voltages at 2 K. Because of device gain, the effective dark current (equivalent photon rate) is less than 3 e(-)s(-1) under all operating conditions. The effective read noise (equivalent photon noise) is found to be less than 12 electrons under all operating conditions and for integration times between 0.05 and 100 seconds

A New Large-Well 1024x1024 Si:As Detector for the Mid-Infrare

We present a description of a new 1024x1024 Si:As array designed for ground-based use from 5 - 28 microns. With a maximum well depth of 5e6 electrons, this device brings large-format array technology to bear on ground-based mid-infrared programs, allowing entry to the megapixel realm previously only accessible to the near-IR. The multiplexer design features switchable gain, a 256x256 windowing mode for extremely bright sources, and it is two-edge buttable. The device is currently in its final design phase at DRS in Cypress, CA. We anticipate completion of the foundry run in the beginning of 2006. This new array will enable wide field, high angular resolution ground-based follow up of targets found by space-based missions such as the Spitzer Space Telescope and the Widefield Infrared Survey Explorer (WISE).Comment: 8 pages, 9 figures, 2005 San Diego SPI

Safety of Thioguanine in Pediatric Inflammatory Bowel Disease:A Multi-Center Case Series

Thioguanine (TG) has been shown as a safe alternative in adults with inflammatory bowel disease (IBD) who did not tolerate conventional thiopurines [azathioprine (AZA)/mercaptopurine]. However, data in pediatric IBD are scarce. Therefore, we aimed to assess the safety of TG as maintenance therapy. METHODS: A retrospective, multicenter cohort study of children with IBD on TG was performed in the Netherlands. TG-related adverse events (AE) were assessed and listed according to the common terminology criteria for AE. RESULTS: Thirty-six children with IBD (median age 14.5 years) on TG (median dose 15 mg/day) were included in 6 centers. Five AE occurred during follow-up [pancreatitis (grade 3), hepatotoxicity (grade 3) (n = 2), Clostridium difficile infection (grade 2), and abdominal pain (grade 2)]. All patients (n = 8) with a previously AZA-induced pancreatitis did not redevelop pancreatitis on TG. CONCLUSIONS: In pediatric IBD, TG seems a safe alternative in case of AZA-induced pancreatitis. Further research assessing long-term TG-related safety and efficacy is needed

Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation

Background PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children. Methods Here, we present the first case of a child who developed PNP on a PTLD after small bowel transplantation because of a severe genetic protein-losing enteropathy. Results The patient in this case report had a severe stomatitis, striate palmoplantar keratoderma, and lichenoid skin lesions. In addition, she had marked esophageal involvement. She had lung pathology due to recurrent pulmonary infections and ventilator injury. Although we found no evidence of BO, she died from severe pneumonia and respiratory failure at the age of 12 years. Conclusion It is exceptional that, despite effective treatment of the PTLD, the girl survived 5 years after her diagnosis of PNP. We hypothesize that the girl survived relatively long after the PNP diagnosis due to strong T-cell suppressive treatments for her small bowel transplantation

Ferric carboxymaltose versus ferrous fumarate in anemic children with inflammatory bowel disease:the POPEYE randomized controlled clinical trial

OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD).STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8 to 18 with IBD and anemia (defined as hemoglobin (Hb) z-score &lt; -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary endpoint was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline.RESULTS: We randomized 64 patients (33 IV iron; 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P=0.01). At 3- and 6-months follow-up, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3 and 6 months after initiation of iron therapy (overall P=0.97).CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral or IV therapy. The increase of Hb over time was comparable in both treatment groups.TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].</p

Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease

Contains fulltext : 96924.pdf (publisher's version ) (Open Access)BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients

Randomised clinical trial: First-line infliximab biosimilar is cost-effective compared to conventional treatment in paediatric Crohn's disease

Background: Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed. Aim: To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease. Methods: We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks. Results: We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03–2.35, p = 0.036). Conclusions: First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease. Trial registration number: NCT02517684

Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations

<p>Abstract</p> <p>Background</p> <p>Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of <it>ATP7B </it>mutations and to more completely characterize WND in China.</p> <p>Methods</p> <p>The coding and promoter regions of the <it>ATP7B </it>gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old).</p> <p>Results</p> <p>Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).</p> <p>Conclusions</p> <p>We identified 14 novel mutations and found that the spectrum of mutations of <it>ATP7B </it>in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.</p