Interim estimates of 2013/14 vaccine effectiveness against influenza A(H1N1)pdm09 from Canada s sentinel surveillance network, January 2014.

The 2013/14 influenza season to date in Canada has been characterised by predominant (90%) A(H1N1)pdm09 activity. Vaccine effectiveness (VE) was assessed in January 2014 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically-attended laboratory-confirmed influenza A(H1N1)pdm09 infection was 74% (95% CI: 58-83). Relative to vaccine, A(H1N1)pdm09 viruses were antigenically similar and genetically well conserved, with most showing just three mutations across the 50 amino acids comprising antigenic sites of the haemagglutinin protein.

Detection of FLASH-radiotherapy tissue sparing in a 3D-spheroid model using DNA damage response markers.

PURPOSE: The oxygen depletion hypothesis has been proposed as a rationale to explain the observed phenomenon of FLASH-radiotherapy (FLASH-RT) sparing normal tissues while simultaneously maintaining tumor control. In this study we examined the distribution of DNA Damage Response (DDR) markers in irradiated 3D multicellular spheroids to explore the relationship between FLASH-RT protection and radiolytic-oxygen-consumption (ROC) in tissues. METHODS: Studies were performed using a Varian Truebeam linear accelerator delivering 10 MeV electrons with an average dose rate above 50 Gy/s. Irradiations were carried out on 3D spheroids maintained under a range of O2 and temperature conditions to control O2 consumption and create gradients representative of in vivo tissues. RESULTS: Staining for pDNA-PK (Ser2056) produced a linear radiation dose response whereas γH2AX (Ser139) showed saturation with increasing dose. Using the pDNA-PK staining, radiation response was then characterised for FLASH compared to standard-dose-rates as a function of depth into the spheroids. At 4 °C, chosen to minimize the development of metabolic oxygen gradients within the tissues, FLASH protection could be observed at all distances under oxygen conditions of 0.3-1 % O2. Whereas at 37 °C a FLASH-protective effect was limited to the outer cell layers of tissues, an effect only observed at 3 % O2. Modelling of changes in the pDNA-PK-based oxygen enhancement ratio (OER) yielded a tissue ROC g0-value estimate of 0.73 ± 0.25 µM/Gy with a km of 5.4 µM at FLASH dose rates. CONCLUSIONS: DNA damage response markers are sensitive to the effects of transient oxygen depletion during FLASH radiotherapy. Findings support the rationale that well-oxygenated tissues would benefit more from FLASH-dose-rate protection relative to poorly-oxygenated tissues.

Case of vaccine-associated measles five weeks post-immunisation, British Columbia, Canada, October 2013.

We describe a case of vaccine-associated measles in a two-year-old patient from British Columbia, Canada, in October 2013, who received her first dose of measles-containing vaccine 37 days prior to onset of prodromal symptoms. Identification of this delayed vaccine-associated case occurred in the context of an outbreak investigation of a measles cluster.

Interim estimates of influenza vaccine effectiveness in 2012/13 from Canada's sentinel surveillance network, January 2013.

The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13-66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.

Clinical Best Practices for Radiation Safety During Lutetium-177 Therapy.

IMPORTANCE: 177 Lu therapy as part of theranostic treatment for cancer is expanding but it can be a challenge for sites with limited radiation protection staff to implement the radiation safety program required for therapeutic nuclear medicine. OBJECTIVE: To increase the adoption of 177 Lu therapy, especially in smaller centers and clinics, by providing a collection of radiation safety best practices and operational experience. To provide a resource for radiation safety officers supporting the implementation of a 177 Lu therapy program. METHODS: A panel of 11 radiation safety professionals representing sites across Canada and the United States with experience delivering 177 Lu therapy was assembled and discussed their responses to a list of questions focused on the following radiation safety topics: facility layout and design; radiation safety program; and drug management and patient care. RESULTS: A comprehensive set of best practice guidelines for clinical radiation safety during 177 Lu therapy has been developed based on the collective operational experience of a group of radiation safety professionals. Significant findings included that 177 Lu therapy is often safely administered in unshielded rooms, that staff radiation exposure associated with 177 Lu therapy is minimal relative to other nuclear medicine programs, and that some relatively simple preparation in advance including papering of common surfaces and planning for incontinence can effectively control contamination during therapy. CONCLUSION: The guidance contained in this paper will assist radiation safety professionals in the implementation of safe, effective 177 Lu therapy programs, even at smaller sites with limited to no experience in therapeutic nuclear medicine.

Quantitative evaluation of PSMA PET imaging using a realistic anthropomorphic phantom and shell-less radioactive epoxy lesions.

BACKGROUND: Positron emission tomography (PET) with prostate specific membrane antigen (PSMA) have shown superior performance in detecting metastatic prostate cancers. Relative to [18F]fluorodeoxyglucose ([18F]FDG) PET images, PSMA PET images tend to visualize significantly higher-contrast focal lesions. We aim to evaluate segmentation and reconstruction algorithms in this emerging context. Specifically, Bayesian or maximum a posteriori (MAP) image reconstruction, compared to standard ordered subsets expectation maximization (OSEM) reconstruction, has received significant interest for its potential to reach convergence with minimal noise amplifications. However, few phantom studies have evaluated the quantitative accuracy of such reconstructions for high contrast, small lesions (sub-10 mm) that are typically observed in PSMA images. In this study, we cast 3 mm-16-mm spheres using epoxy resin infused with a long half-life positron emitter (sodium-22; 22Na) to simulate prostate cancer metastasis. The anthropomorphic Probe-IQ phantom, which features a liver, bladder, lungs, and ureters, was used to model relevant anatomy. Dynamic PET acquisitions were acquired and images were reconstructed with OSEM (varying subsets and iterations) and BSREM (varying ß parameters), and the effects on lesion quantitation were evaluated. RESULTS: The 22Na lesions were scanned against an aqueous solution containing fluorine-18 (18F) as the background. Regions-of-interest were drawn with MIM Software using 40% fixed threshold (40% FT) and a gradient segmentation algorithm (MIM's PET Edge+). Recovery coefficients (RCs) (max, mean, peak, and newly defined "apex"), metabolic tumour volume (MTV), and total tumour uptake (TTU) were calculated for each sphere. SUVpeak and SUVapex had the most consistent RCs for different lesion-to-background ratios and reconstruction parameters. The gradient-based segmentation algorithm was more accurate than 40% FT for determining MTV and TTU, particularly for lesions [Formula: see text] 6 mm in diameter (R2 = 0.979-0.996 vs. R2 = 0.115-0.527, respectively). CONCLUSION: An anthropomorphic phantom was used to evaluate quantitation for PSMA PET imaging of metastatic prostate cancer lesions. BSREM with ß = 200-400 and OSEM with 2-5 iterations resulted in the most accurate and robust measurements of SUVmean, MTV, and TTU for imaging conditions in 18F-PSMA PET/CT images. SUVapex, a hybrid metric of SUVmax and SUVpeak, was proposed for robust, accurate, and segmentation-free quantitation of lesions for PSMA PET.

A new RT-PCR assay specific for influenza A(H2), multiplexed with an assay specific for HPAI A(H5N1).

Worldwide efforts are ongoing to improve influenza pandemic preparedness, including from the perspective of the clinical virology laboratory. In particular, much work has been devoted to the development of diagnostic assays targeted at the Highly Pathogenic Avian Influenza (HPAI) A(H5N1); much less efforts have been devoted to the A(H2) subtype. Yet, A(H2) subtype has a proven capacity to cause pandemics and is among the subtypes prioritized for surveillance and control. Although the human A(H2N2) virus that caused the pandemic of 1957 no longer circulates, many related avian A(H2) viruses circulate in avian population and could conceivably adapt to infect humans and cause a new pandemic. In this study the design and development of an RT-PCR assay specific for A(H2) subtype is presented. It is shown that the assay is highly sensitive and specific, able to detect human and avian A(H2) viruses, and can be incorporated into a multiplex assay with another previously described assay for HPAI A(H5N1).

Fingerprinting Mean Composition of Lithium Polysulfide Standard Solutions by Applying High-Energy Resolution Fluorescence Detected X-ray Absorption Spectroscopy.

In a lithium/sulfur (Li/S) battery, the reduction of sulfur during discharge involves a particular mechanism, where the active material successively dissolves into the electrolyte to form lithium polysulfide intermediate species (Li2Sx), with x being a function of the state of charge. In this work, sulfur K-edge resonant inelastic X-ray scattering measurements were performed for the characterization of different Li2Sx polysulfide standard solutions. High-energy resolution fluorescence detected X-ray absorption spectroscopy allowed clear separation the pre-edge absorption peak corresponding to terminal sulfur atoms from the main absorption peak due to internal atoms and allowed quantitative evaluation of the evolution of the peak area ratio as a function of the polysulfide chain length. Results of this experimental work demonstrate that the normalized area of the pre-edge is a reliable fingerprint of the Li2Sx mean chain length in agreement with recent theoretical predictions. As a perspective, this work confirms that operando HERFD XAS can be used to differentiate mean polysulfide composition, which is key issue in the characterization of Li/S cells.

Massive splenomegaly due to B-cell lymphoma: A case report.

INTRODUCTION: Massive splenomegaly is indicated by spleen weight exceeding 1000 g and largest spleen dimension greater than 20 cm Poulin et al. (1998). In many cases, splenectomy is the treatment of choice for massive splenomegaly because it releases the pressure on adjacent organs and also provides a definitive histopathological diagnosis of the underlying cause Iriyama et al. (2010), Radhakrishnan (2018). PRESENTATION OF CASE: Herein we present a clinical case of disseminated diffuse large B - cell lymphoma, clinical stage IV, with massive splenomegaly. A 53 - year old man complaining of unintentional major weight loss, palpable abdominal mass in the left hemiabdomen and cervical lymphadenopathy, was admited to Department of abdominal surgery, UMC Ljubljana. Abdominal CT scan showed massive spleen, enlarged retroperitoneal and upper mediastinal lymph nodes and cervical lymphadenopathy. Splenectomy was performed and spleen was sent on histological analysis. Operation and postoperative course were uneventful. Spleen specimen weighed 5034 g (6% of patient body weight) and measured 33 × 24 × 10 cm. Histological and immunohistochemical analysis set the diagnosis of diffuse large B - cell lymphoma. Patients received 5 cycluses of R-CHOP chemotherapy and 2 cycluses of prophylactic intrathecal chemotherapy postoperatively. DISCUSSION: Splenomegaly in combination with weight loss and malaise is very suggestive of underlying neoplastic condition and therefore requires further diagnostic investigations Han et al. (2008). Splenectomy in combination with adjuvant chemotherapy is the treatment of choice in case of spleen infiltration rith tumorous cells of B-cell lymphoma. However there are other possibilities in diagnosing and treatment of massive splenomegaly, including percutaneous image guided splenic needle biopsy and splenic artery embolisation prior to splenectomy. CONCLUSION: Our aim with this case report is to present splenectomy in conjuction with chemotherapy as a safe option of treatment for massive splenomegaly due to B-cell lymphoma infiltration.

Effects of 10 MV and Flattening-Filter-Free Beams on Peripheral Dose in a Cohort of Pediatric Patients.

PURPOSE: To assess the effect of flattening-filter-free (FFF) and 10 MV radiation therapy beams on the peripheral dose received by a population of pediatric patients undergoing volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS: Twenty-six previously delivered 6 MV flattened VMAT pediatric radiation therapy treatments plans were replanned with 6 MV flattened, 6 MV FFF, and 10 MV FFF VMAT. Monte Carlo simulation code EGSnrc was used in conjunction with a measurement-based model to obtain 3-dimensional dose distributions. Peripheral dose delivered by FFF beams was compared with that delivered by 6 MV flattened beams. A statistical analysis was performed to determine whether certain clinical factors (eg, target volume, location) were associated with a change in integral relative radiation dose. Neutron dose measurements assessed the neutron contribution from the 6 MV flattened and 10 MV FFF x-ray beams. RESULTS: Both the 6 MV FFF and 10 MV FFF beams delivered significantly lower peripheral radiation doses than 6 MV flattened (P < .01). The dose reduction was of 3.9% (95% confidence interval [CI] 2.1-5.7) and 9.8% (95% CI, 8.0-11.6) at 5 cm from the PTV and 21.9% (95% CI, 13.7-30.1) and 25.6% (95% CI, 17.6-33.6) at 30 cm for 6 MV FFF and 10 MV FFF beams, respectively. The clinical factors examined did not have a significant effect on the relative magnitude of the peripheral dose reduction. The upper limit on the neutron dose was determined to be 203 µSv for the 6 MV flattened and 522 µSv for the 10 MV FFF beam. CONCLUSIONS: Both FFF beams significantly (P < .01) reduced the peripheral dose. 10 MV FFF was more effective at reducing peripheral dose at distances <5 cm from the PTV edge. The neutron doses delivered by all beams were <1% compared with the photon doses. 10 MV FFF should be used to minimize peripheral dose.

Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.

To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.

Design of a single tube RT-PCR assay for the diagnosis of human infection with highly pathogenic influenza A(H5) viruses.

Concerns about emergence of a pandemic strain of influenza have been increasing. The strains of highly pathogenic influenza A(H5N1) currently circulating are considered among the most plausible candidates for giving rise to a pandemic strain. In this study the design and development of a RT-PCR assay specific for these highly pathogenic influenza A(H5) strains is presented. This is achieved in part by the design of a primer targeting the coding region for the protease cleavage site of the hemagglutinin, and another primer derived from a pan-hemagglutinin RT-PCR assay also presented in this study. It is shown that the HPAI A(H5) specific assay amplifies only the nucleic acids of highly pathogenic A(H5), with a high sensitivity.

Inactivation of Norovirus by ozone gas in conditions relevant to healthcare.

We evaluated the ability of ozone gas to inactivate Norovirus and its animal surrogate feline calicivirus (FCV) in dried samples placed at various locations within a hotel room, a cruise liner cabin and an office. Norovirus was measured by quantitative reverse transcriptase real-time polymerase chain reaction (QRT-PCR) assay, and FCV by a combination of QRT-PCR and virus infectivity assays. We were able to reduce the concentration of infectious FCV by a factor of more than 10(3), and in some cases beyond detection, under optimal conditions of ozone exposure with less than an hour of total operation. QRT-PCR assays indicated similar decreases in both viral RNAs. Virus-containing samples dried onto hard surfaces (plastic, steel and glass), and soft surfaces such as fabric, cotton and carpet, were equally vulnerable to the treatment. Our results show that Norovirus can be inactivated by exposure to ozone gas from a portable commercial generator in settings such as hotel rooms, cruise ship cabins and healthcare facilities.

The diagnosis of genital herpes - beyond culture: An evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology.

Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR) and conventional and type-specific serology (TSS). PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners.

Development and characterization of a tissue equivalent plastic scintillator based dosimetry system.

High precision techniques in radiation therapy, such as intensity modulated radiation therapy, offer the potential for improved target coverage and increased normal tissue sparing compared with conformal radiotherapy. The complex fluence maps used in many of these techniques, however, often lead to more challenging quality assurance with dose verification being labor-intensive and time consuming. A prototype dose verification system has been developed using a tissue equivalent plastic scintillator that provides easy-to-acquire, rapid, digital dose measurements in a plane perpendicular to the beam. The system consists of a water-filled Lucite phantom with a scintillator screen built into the top surface. The phantom contains a silver coated plastic mirror to reflect scintillation light towards a viewing window where it is captured using a charge coupled device camera and a personal computer. Optical photon spread is removed using a microlouvre optical collimator and by deconvolving a glare kernel from the raw images. A characterization of the system was performed that included measurements of linear output response, dose rate dependence, spatial linearity, effective pixel size, signal uniformity and both short- and long-term reproducibility. The average pixel intensity for static, regular shaped fields between 3 cm X 3 cm and 12 cm x 12 cm imaged with the system was found to be linear in the dose delivered with linear regression analysis yielding a correlation coefficient r2 > 0.99. Effective pixel size was determined to be 0.53 mm/pixel. The system was found to have a signal uniformity of 5.6% and a long-term reproducibility/stability of 1.7% over a 6 month period. The system's ability to verify a dynamic treatment field was evaluated using 60 degrees dynamic wedged fields and comparing the results to two-dimensional film dosimetry. Results indicate agreement with two-dimensional film dosimetry distributions within 8% inside the field edges. With further development, this system promises to provide a fast, directly digital, and tissue equivalent alternative to current dose verification systems.

A comparison of two commercial treatment-planning systems to IMRT.

This study compared the clinical functionality of BrainSCAN (BrainLAB) and Helios (Eclipse, Varian) for intensity-modulated radiation therapy (IMRT) treatment planning with the aim of identifying practical and technical issues. The study considered implementation and commissioning, dose optimization, and plan assessment. Both systems were commissioned for the same 6 MV photon beam equipped with a high-resolution multileaf collimator (Varian Millennium 120 leaf). The software was applied to three test plans having identical imaging and contour data. Analysis considered 3D axial dose distributions, dose-volume histograms, and monitor unit calculations. Each system requires somewhat different input data to characterize the beam prior to use, so the same data cannot be used for commissioning. In addition, whereas measured beam data was entered directly into Helios with minimal data processing, the BrainSCAN system required configured beam data to be sent to BrainLAB before clinical use. One key difference with respect to system commissioning was that BrainSCAN required high resolution data, which necessitated the use of detectors with small active volumes. This difference was found to impact on the ability of the systems to accurately calculate dose for highly modulated fields, with BrainSCAN being more successful than Helios. In terms of functionality, the BrainSCAN system uses a dynamically penalized likelihood inverse planning algorithm and calculates four plans at once with various relative weighting of the planning target and organ-at-risk volumes. Helios uses a gradient algorithm that allows the user to make changes to some of the input parameters during optimization. An analysis of the dosimetry output shows that, although the systems are different in many respects, they are each capable of producing substantially equivalent dose plans in terms of target coverage and normal tissue sparing.

Effects of thyroid-stimulating hormone on the replicative cycle of vesicular stomatitis virus in primary cultured sheep thyroid cells.

Sheep thyroid cells in primary culture are highly sensitive to thyroid stimulating hormone (TSH). We infected thyroid cells with vesicular stomatitis virus (VSV) in the course of studies on cell polarity, and we found that TSH augmented the speed of the replicative cycle of VSV but did not affect the final yield of the virus. Three hours post-infection, at a multiplicity of infection of 10, the virus was detected in the cell layer of the cultures incubated with TSH but not in those without TSH. Five hours post-infection, there was a 100-fold increase in the medium in the yield of VSV and a 60-fold increase in the cell-associated virus in the TSH-treated cells compared with the cells without TSH. We found that the early stages of infection were accelerated by TSH. This effect appears to be due, at least in part, to increased processing in the lysosomes, thus allowing deposition of the transcriptionally-active nucleocapsid into the cytoplasm. These studies show that TSH is critically involved in the infectivity of VSV and that by manipulating cell culture conditions, an increased rate of virus production can be achieved.

Portal imaging for evaluation of daily on-line setup errors and off-line organ motion during conformal irradiation of carcinoma of the prostate.

PURPOSE: To use portal imaging to measure daily on-line setup error and off-line prostatic motion in patients treated with conformal radiotherapy to determine an optimum planning target volume (PTV) margin incorporating both setup error and organ motion. RESULTS: A total of 2549 portal images from 33 patients were acquired over the course of the study. Of these patients, 23 were analyzed for setup errors while the remaining 10 were analyzed for prostatic motion. Setup errors were characterized by standard deviations of 1.8 mm in the anterior-posterior (AP) direction and 1.4 mm in the superior-inferior (SI) direction. Displacements due to prostatic motion, with standard deviations of 5.8 mm AP and 3.3 mm SI, were found to be more significant than setup errors. CONCLUSIONS: Taking into account both setup errors and target organ motion, optimum PTV margins to ensure 95% coverage are 10.0 mm AP and 5.9 mm SI. The portal imaging protocol established in this study allows radiation therapists to accept or adjust a treatment setup based upon daily on-line image matching results. The successful localization of radiopaque fiducial markers on a significant number of portal images acquired in the study gives hope that more accurate on-line targeting verification may soon be possible through the visualization of the prostate itself as opposed to the surrounding bony structures of the pelvis.

Electrophoretic migration of adenovirus hexon under non-denaturing conditions.

While SDS-PAGE/immunoblotting is a valuable approach for the characterization of monoclonal antibodies, the denaturing conditions involved can compromise the recognition of conformational epitopes. This report demonstrates that a group specific epitope on adenovirus hexon can be recognized by immunoblotting following SDS-PAGE provided that samples are not boiled prior to electrophoresis. Under these conditions, multiple bands corresponding to native forms of hexon were detected above the position of the denatured hexon monomer. Among representative serotypes of subgroups A, B and F, two predominant bands, corresponding to hexon trimers and 'group of nine' hexons (GONs), were routinely observed. In contrast, higher order structures, in addition to trimers and GONs, were characteristic of subgroup C adenoviruses. These serotypic differences in stability of hexon structures may reflect differences in protein-protein interactions within the corresponding virions.