Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas with Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE/OBJECTIVE: The proximity or overlap of PTV and OAR poses a major challenge in SBRT of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether Simultaneously Integrated Boost (SIB) and Protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. MATERIALS/METHODS: A multiparametric specification of desired target doses (GTVD50%, GTVD99%, PTVD95%, PTV0.5cc) with two prescription doses of GTVD50%=5×9.2Gy (46Gy) and GTVD50%=8×8.25Gy (66Gy) and OAR limits were distributed with planning CT and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, re-planning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2% and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSION: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

Prevalence of rotavirus and human bocavirus in immunosuppressed individuals after renal transplantation in the Northern Region of Brazil.

Immunosuppressive therapy causes severe impairment of host defense and diarrhea is a frequent complication in renal transplant recipients. This study aimed to describe the occurrence of Rotavirus A (RVA) and Human Bocavirus (HBoV) in fecal samples of immunosuppressed patients submitted to renal transplantation during posttransplant follow-up. A longitudinal study was carried out involving a 25-patient cohort, selected for kidney transplantation. A total of 126 fecal samples were collected between May 2014 and May 2016. Molecular techniques were used to detect and characterize circulating RVA and HBoV genotypes and statistical analysis were applied to verify the association between epidemiological and clinical characteristics. The prevalence of RVA and HBoV was 24% (6/25) and 40% (10/25), respectively. Among RVA and HBoV positive cases, the majority was female; did not conduct water treatment nor had adequate sewage facilities. The most detected genotypes were RVA G3 (62.5%) and HBoV-3 (95%). Phylogenetic analysis of HBoV strains indicated that studied samples were similar to those found in Asian and American countries. The present study point out the circulation of these viral agents among immunosuppressed individuals and these findings will enable the construction of new knowledge and care perspectives on the cause of diarrhea in this population.

Molecular epidemiology of human bocavirus in children with acute gastroenteritis from North Region of Brazil.

PURPOSE: Human bocavirus (HBoV) is a DNA virus that is mostly associated with respiratory infections. However, because it has been found in stool samples, it has been suggested that it may be a causative agent for human enteric conditions. This underpins the continuous search for HBoVs, especially after the introduction of the rotavirus vaccine due to acute gastroenteritis cases related to emergent viruses, as HBoVs are more likely to be found in this post-vaccine scenario. Therefore, the aim of this study is to demonstrate the prevalence of HBoV in children aged less than 10 years with acute gastroenteritis in Brazil from November 2011 to November 2012. METHODOLOGY: Stool samples from hospitalized children ≤10 years old who presented symptoms of acute gastroenteritis were analysed for the presence of rotavirus A (RVA) by an enzyme-linked immunosorbent assay (ELISA), and for HBoV DNA by nested PCR. RESULTS: HBoV positivity was detected in 24.0 % (54/225) of samples. Two peaks of HBoV detection were observed in November 2011 and from July to September 2012. Co-infections between HBoV and rotavirus A were identified in 50.0 % (27/54) of specimens. Phylogenetic analysis identified the presence of HBoV-1 (94.8 %), HBoV-2 (2.6 %) and HBoV-3 (2.6 %) species, with only minor variations among them. CONCLUSION: Our findings provide evidence for the circulation of most HBoV genotypes (except HBoV-4) in the North Region of Brazil at a considerable rate and further investigations are necessary to improve our knowledge in the context of HBoV infections and their role in gastrointestinal diseases.

Emergence of G12P[6] rotavirus strains among hospitalised children with acute gastroenteritis in Belém, Northern Brazil, following introduction of a rotavirus vaccine.

Species A rotavirus still remains a major cause of acute gastroenteritis in infants and young children. Globally, six genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8]) account for >90% of circulating strains; however, genotype G12 in combination with P[6] or P[9] has been detected at increasing rates. We sought to broaden our knowledge about the rotavirus strains circulating during the early post-vaccine-introduction period. Stool samples were obtained from children hospitalised for acute gastroenteritis in Belém, Northern Brazil, from May 2008 to May 2011 and examined by reverse transcription polymerase chain reaction and nucleotide sequencing. A total of 122 out of the original 1076 rotavirus strains were judged to be non-typeable in the first analysis and were therefore re-examined. G2P[4] was the most prevalent genotype (58.0%), followed by G1P[8] (16.9%), and G12P[6] (7.5%). G12P[6] strains were identified at similar rates during the first (2.5%) and second (3.9%) years, and the rate jumped to 15.6% in the third year. Analysis of VP7 sequences of the G12P[6] strains showed that they belonged to lineage III. In addition, co-circulating G12P[6] strains displaying long and short RNA patterns were found to belong to the Wa-like and DS-1-like constellation, respectively. Additional unusual circulating strains G12P[9] and G3P[9] were also identified. This hospital-based study showed a high prevalence of G12P[6] strains in the third year of surveillance. Our results highlight the need for continuous longitudinal monitoring of circulating rotavirus strains after introduction of rotavirus vaccines in Brazil and elsewhere.

Analysis of a genotype G3P[9] rotavirus a strain that shows evidence of multiple reassortment events between animal and human rotaviruses.

The species A rotaviruses (RVA) are important gastroenteric pathogens that infect humans and animals. RVA genotype G3P[9] has been described in human-animal reassortment events, and the complexity of its hosts motivates the genetic investigation of this strain. Therefore, the aim of this study is to analyse a G3P[9] sample that was detected in a child with acute gastroenteritis. The 1A3739 sample featured the constellation G3P[9]-I18-R3-C3-Mx-A19-N3-T3-E3-H6. The sequence for VP3 gene was not obtained. The phylogeny showed a closer relationship among genes VP7, VP1, NSP3, NSP4, and NSP5 with genes of animal origin, such as chiropter, alpaca, equine, and simian. In addition, the genes VP6 and NSP1 belong to the new genotypes I18 and A19, respectively. The emergence of strains such as these can interfere with the effectiveness of the RVA vaccine, and continuous monitoring is therefore important. Additional studies are needed to determine the evolutionary source and to identify a possible reservoir of RVA in nature.

Detection of the VP6 gene of group F and G rotaviruses in broiler chicken fecal samples from the Amazon region of Brazil.

The aim of this study was to detect rotavirus F (RVF) and rotavirus G (RVG) in fecal specimens of broiler chickens in Brazil. During 2008 and 2011, a total of 85 fecal samples were collected. The viral genome was extracted, followed by polyacrylamide gel electrophoresis (PAGE), reverse transcription polymerase chain reaction (RT-PCR), and nucleotide sequencing. Samples were screened for rotaviruses by PAGE, and RVF and RVG genome banding patterns were not seen. Using RT-PCR, it was found that 9.4 % (8/85) of the pools contained RVF, whereas 10.6 % (9/85) contained RVG. The predicted amino acid sequences of RVF and RVG from Brazilian samples were 94.4-95.7 % and 96.8-96.9 % identical, respectively, to those of prototypes from Germany. The detection of RVF and RVG in this study provides important epidemiological data about the simultaneous circulation of rotaviruses affecting broiler flocks in the Amazon region of Brazil.

Radiochromic film dosimetry with flatbed scanners: a fast and accurate method for dose calibration and uniformity correction with single film exposure.

Film dosimetry is an attractive tool for dose distribution verification in intensity modulated radiotherapy (IMRT). A critical aspect of radiochromic film dosimetry is the scanner used for the readout of the film: the output needs to be calibrated in dose response and corrected for pixel value and spatial dependent nonuniformity caused by light scattering; these procedures can take a long time. A method for a fast and accurate calibration and uniformity correction for radiochromic film dosimetry is presented: a single film exposure is used to do both calibration and correction. Gafchromic EBT films were read with two flatbed charge coupled device scanners (Epson V750 and 1680Pro). The accuracy of the method is investigated with specific dose patterns and an IMRT beam. The comparisons with a two-dimensional array of ionization chambers using a 18 x 18 cm2 open field and an inverse pyramid dose pattern show an increment in the percentage of points which pass the gamma analysis (tolerance parameters of 3% and 3 mm), passing from 55% and 64% for the 1680Pro and V750 scanners, respectively, to 94% for both scanners for the 18 x 18 open field, and from 76% and 75% to 91% for the inverse pyramid pattern. Application to an IMRT beam also shows better gamma index results, passing from 88% and 86% for the two scanners, respectively, to 94% for both. The number of points and dose range considered for correction and calibration appears to be appropriate for use in IMRT verification. The method showed to be fast and to correct properly the nonuniformity and has been adopted for routine clinical IMRT dose verification.

Use of biomarkers of sub-clinical infection, nutrition and neonatal maturity to interpret plasma retinol in Nigerian neonates.

Using the World Health Organization criterion, the prevalence of sub-clinical vitamin A deficiency can be assessed using plasma retinol concentrations <0.7 micromol/l. However, plasma retinol can be depressed by infection; thus, the use of this criterion alone may overestimate deficiency. In the present study, we investigated the usefulness of the acute-phase proteins (APP) alpha1-antichymotrypsin (ACT) and alpha1-acid glycoprotein (AGP), plasma carotenoids and anthropometric and gestational indices to interpret plasma retinol in the blood of 192 apparently healthy Nigerian neonates collected randomly during days 1-20 postpartum. The mean weight (2.64 kg) and length (0.458 m) of the neonates and plasma concentrations (geometric mean, micromol/l) of retinol (0.54), alpha-carotene (0.072), ss-carotene (0.076) and lutein (0.080) were low. The prevalence of vitamin A deficiency was 72 %, indicating a severe public health problem. Babies who were of low birth weight (P<0.003) or premature and low birth weight (P<0.023) had significantly lower retinol concentrations than full-term normal weight babies. Thirty-two neonates had abnormal ACT and forty-four abnormal AGP concentrations. Positive correlations between retinol and ACT (r 0.186, P=0.05) and AGP (r 0.31, P=0.0001) during days 1-5 may be due to the increasing plasma retinol from maternal milk and a coincidental increasing capacity to synthesise APP. Subsequently, negative correlations between retinol and ACT (r -0.28, P=0.02) and AGP (r -0.29, P=0.018) from day 6 onwards reflected the continuing increase in plasma retinol, but no further increase in the APP. Overall, weight, ACT, lutein and age explained 30 % of the variance in retinol, but lutein was the most significant (r(2) 0.18, P<0.0001). Hence, the distribution of plasma retinol concentrations in this group of neonates was more strongly linked with nutrition (via the surrogate marker lutein) than infection.

Integrating waveguide biosensor.

A capillary biosensor is demonstrated which uses the waveguiding properties of the capillary to integrate the signal over an increased surface area without simultaneously increasing the background noise from the detector. This biosensor achieves limits of detection of 30-50 pg/mL in immunoassays using a diode laser for excitation and a PMT for detection. This is approximately 2 orders of magnitude greater sensitivity than was achieved using the same immunoassay reagents in a fiber optic biosensor or a planar array biosensor. Two different approaches to using the capillaries as immunosensors are described, either of which could be adapted for multianalyte sensing.

Multilayer sol-gel membranes for optical sensing applications: single layer pH and dual layer CO(2) and NH(3) sensors.

Organo-silica sol-gel membranes have been prepared and demonstrated in a single layer format for pH measurement and multiple-layer format for both carbon dioxide and ammonia. The sensors are simple and versatile since the same chemistry and membranes are used for each sensor. The sensors use hydroxypyrenetrisulfonic acid (HPTS) as the indicator immobilized in a base-catalyzed sol-gel containing poly(dimethyl)siloxane, aminopropyltriethoxysilane (APTES) and tetraethylorthosilicate (TEOS). This indicator gel is over coated with a hydrophobic sol-gel to reduce cross reactivity to pH when either CO(2) or NH(3) are examined. The gels are very stable and the sensors retain response up to a 12-month period. Sensors can be stored in buffer or dry without loss of function and have response times to that are comparable to literature values.