bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a new commercial Monte Carlo dose calculation algorithm for electron beams
Authors: Vandervoort Eric J. , Tchistiakova Ekaterina , La Russa Daniel J. , Cygler Joanna E. 
Published: January 2014

Purpose:In this report the authors present the validation of a Monte Carlo dose calculation algorithm (XiO EMC from Elekta Software) for electron beams.Methods:Calculated and measured dose distributions were compared for homogeneous water phantoms and for a 3D heterogeneous phantom meant to approximate the geometry of a trachea and spine. Comparisons of measurements and calculated data were performed using 2D and 3D gamma index dose comparison metrics.Results:Measured outputs agree with calculated values within estimated uncertainties for standard and extended SSDs for open applicators, and for cutouts, with the exception of the 17 MeV electron beam at extended SSD for cutout sizes smaller than 5 × 5 cm2. Good agreement was obtained between calculated and experimental depth dose curves and dose profiles (minimum number of measurements that pass a 2%/2 mm agreement 2D gamma index criteria for any applicator or energy was 97%). Dose calculations in a heterogeneous phantom agree with radiochromic film measurements (>98% of pixels pass a 3 dimensional 3%/2 mm γ‐criteria) provided that the steep dose gradient in the depth direction is considered.Conclusions:Clinically acceptable agreement (at the 2%/2 mm level) between the measurements and calculated data for measurements in water are obtained for this dose calculation algorithm. Radiochromic film is a useful tool to evaluate the accuracy of electron MC treatment planning systems in heterogeneous media.
Plan averaging for multicriteria navigation of sliding window IMRT and VMAT
Authors: Craft David , Papp Dávid , Unkelbach Jan 
Published: January 2014

Purpose:To describe a method for combining sliding window plans [intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT)] for use in treatment plan averaging, which is needed for Pareto surface navigation based multicriteria treatment planning.Methods:The authors show that by taking an appropriately defined average of leaf trajectories of sliding window plans, the authors obtain a sliding window plan whose fluence map is the exact average of the fluence maps corresponding to the initial plans. In the case of static‐beam IMRT, this also implies that the dose distribution of the averaged plan is the exact dosimetric average of the initial plans. In VMAT delivery, the dose distribution of the averaged plan is a close approximation of the dosimetric average of the initial plans.Results:The authors demonstrate the method on three Pareto optimal VMAT plans created for a demanding paraspinal case, where the tumor surrounds the spinal cord. The results show that the leaf averaged plans yield dose distributions that approximate the dosimetric averages of the precomputed Pareto optimal plans well.Conclusions:The proposed method enables the navigation of deliverable Pareto optimal plans directly, i.e., interactive multicriteria exploration of deliverable sliding window IMRT and VMAT plans, eliminating the need for a sequencing step after navigation and hence the dose degradation that is caused by such a sequencing step.
Development and Evaluation of a Blocking Enzyme-Linked Immunosorbent Assay and Virus Neutralization Assay To Detect Antibodies to Viral Hemorrhagic Septicemia Virus
Authors: Wilson Anna , Goldberg Tony , Marcquenski Susan , Olson Wendy , Goetz Frederick , Hershberger Paul , Hart Lucas , Toohey-Kurth Kathy 
Published: January 2014

ABSTRACTViral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV.
Live Oral Salmonella enterica Serovar Typhi Vaccines Ty21a and CVD 909 Induce Opsonophagocytic Functional Antibodies in Humans That Cross-React withS. Paratyphi A andS. Paratyphi B
Authors: Wahid Rezwanul , Zafar Shah J. , McArthur Monica A. , Pasetti Marcela F. , Levine Myron M. , Sztein Marcelo B. 
Published: January 2014

ABSTRACTLive oralSalmonella entericaserovar Typhi vaccine Ty21a induces specific antibodies that cross-react againstSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Paratyphi B, although their functional role in clearance remains unknown. We utilized anin vitroassay with THP-1 macrophages to compare the phagocytosis and survival ofSalmonellaopsonized with heat-inactivated human sera obtained before and after vaccination with Ty21a or a live oralS. Typhi vaccine, CVD 909. Opsonization with postvaccination sera predominantly increased the phagocytosis ofS. Typhi relative to the corresponding prevaccination sera, and increases were also observed withS. Paratyphi A andS. Paratyphi B, albeit of lower magnitudes. Relative to prevaccination sera, opsonization with the postvaccination sera reduced the survival inside macrophages ofS. Typhi but not ofS. Paratyphi A orS. Paratyphi B. Higher anti-S. Typhi O antigen (lipopolysaccharide [LPS]) IgG, but not IgA, antibody titers correlated significantly with postvaccination increases in opsonophagocytosis. No differences were observed between immunization with four doses of Ty21a or one dose of CVD 909. Ty21a and CVD 909 induced cross-reactive functional antibodies, predominantly againstS. Typhi. IgG anti-LPS antibodies may be important in phagocytic clearance of these organisms. Therefore, measurement of functional antibodies might be important in assessing the immunogenicity of a new generation of typhoid and paratyphoid A vaccines. (The CVD 909 study has been registered at ClinicalTrials.gov under registration no. NCT00326443.)
Influence of Frequent Infectious Exposures on General and Varicella-Zoster Virus-Specific Immune Responses in Pediatricians
Authors: Ogunjimi Benson , Smits Evelien , Heynderickx Steven , Van den Bergh Johan , Bilcke Joke , Jansens Hilde , Malfait Ronald , Ramet Jose , Maecker Holden T. , Cools Nathalie , Beutels Philippe , Van Damme Pierre 
Published: January 2014

ABSTRACTReexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4+-naive T cells and showed boosting of CD8+effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.
Comparison of the
illumi
gene Mycoplasma DNA Amplification Assay and Culture for Detection of Mycoplasma pneumoniae
Authors: Ratliff Amy E. , Duffy Lynn B. , Waites Ken B. 
Published: January 2014

ABSTRACT

A loop-mediated isothermal amplification (LAMP) system, the
illumi
gene Mycoplasma DNA amplification assay (Meridian Bioscience, Inc., Cincinnati, OH) was evaluated to determine its analytical sensitivity, specificity, and clinical application in comparison to historic culture in a collection of archived respiratory specimens. The
illumi
gene limit of detection was ≤88 CFU/reaction for 10
Mycoplasma pneumoniae
reference strains. This assay correctly identified 36
M. pneumoniae
reference strains and clinical isolates from various geographic origins, including both of the main subtypes. No cross-reactions were detected with other mycoplasmas, ureaplasmas, other bacterial species, viruses, yeasts, or human DNA. Among 214 respiratory specimens previously cultured for
M. pneumoniae
, when real-time PCR with bidirectional sequencing of the PCR products was used to resolve discrepancies, the sensitivity was 22 of 22 (100%) and the specificity was 190 of 192 (99%). This commercial LAMP assay is a useful rapid method for detecting
M. pneumoniae
in clinical specimens. Additional prospective clinical trials with direct comparison to culture and PCR are warranted.
Eggerthella lenta Bacteremia Complicated by Spondylodiscitis, Psoas Abscess, and Meningitis
Authors: Gardiner B. J. , Korman T. M. , Junckerstorff R. K. 
Published: January 2014

ABSTRACT

Eggerthella lenta
bacteremia is uncommon and generally associated with abdominal sepsis. The organism and its clinical significance have not been well characterized due to historical difficulties with identification. We report a case of severe infection in a paraplegic man complicated by psoas abscess, osteomyelitis, and meningitis and discuss treatment challenges.
Emergence of Q Fever Arthritis in France
Authors: Angelakis Emmanouil , Edouard Sophie , Lafranchi Marie-Alix , Pham Thao , Lafforgue Pierre , Raoult Didier 
Published: January 2014

ABSTRACT

Osteoarticular infection is an uncommon presentation of Q fever. Positron emission tomography (PET) scanning is a valuable tool for the diagnosis of
Coxiella burnetii
graft prosthesis infection and endocarditis. Our objective was to test a series of culture-negative osteoarticular samples using molecular assays for
Coxiella burnetii
. We tested for
C. burnetii
by molecular assays targeting the IS
1111
and the IS
30A
spacer regions, using culture-negative osteoarticular samples obtained in our laboratory between January 2011and December 2012. We examine a total of 1,410 osteoarticular samples, and we observed two cases of arthritis and subacromial bursitis caused by
C. burnetii
. The infections were localized using PET scanning, and the diagnosis was confirmed through serology. For one, a
C. burnetii
strain with a multispacer sequence type 8 genotype was isolated from synovial fluid culture. Q fever articular infections could be undiagnosed because of the long evolution of articular attack, and patients with high antibody titers against
C. burnetii
should be tested using PET scanning to localize the site of infection.
Methylobacterium and Its Role in Health Care-Associated Infection
Authors: Kovaleva Julia , Degener John E. , van der Mei Henny C. 
Published: January 2014

ABSTRACT

Methylobacterium
species are a cause of health care-associated infection, including infections in immunocompromised hosts. The ability of
Methylobacterium
species to form biofilms and to develop resistance to high temperatures, drying, and disinfecting agents may explain the colonization of
Methylobacterium
in the hospital environment in, e.g., endoscopes. Due to its slow growth, it can be easily missed during microbiological surveillance of endoscope reprocessing. The purpose of this minireview is to present an overview of documented infections and cross-contaminations with
Methylobacterium
related to endoscopic procedures and to illustrate the health care-associated relevance of this slow-growing bacterium.
Attenuating Mutations in nsP1 Reveal Tissue-Specific Mechanisms for Control of Ross River Virus Infection
Authors: Stoermer Burrack Kristina A. , Hawman David W. , Jupille Henri J. , Oko Lauren , Minor Marissa , Shives Katherine D. , Gunn Bronwyn M. , Long Kristin M. , Morrison Thomas E. 
Published: January 2014

ABSTRACT

Ross River virus (RRV) is one of a group of mosquito-transmitted alphaviruses that cause debilitating, and often chronic, musculoskeletal disease in humans. Previously, we reported that replacement of the nonstructural protein 1 (nsP1) gene of the mouse-virulent RRV strain T48 with that from the mouse-avirulent strain DC5692 generated a virus that was attenuated in a mouse model of disease. Here we find that the six nsP1 nonsynonymous nucleotide differences between strains T48 and DC5692 are determinants of RRV virulence, and we identify two nonsynonymous nucleotide changes as sufficient for the attenuated phenotype. RRV T48 carrying the six nonsynonymous DC5692 nucleotide differences (RRV-T48-nsP1
6M
) was attenuated in both wild-type and
Rag1
−/−
mice. Despite the attenuated phenotype, RRV T48 and RRV-T48-nsP1
6M
loads in tissues of wild-type and
Rag1
−/−
mice were indistinguishable from 1 to 3 days postinoculation. RRV-T48-nsP1
6M
loads in skeletal muscle tissue, but not in other tissues, decreased dramatically by 5 days postinoculation in both wild-type and
Rag1
−/−
mice, suggesting that the RRV-T48-nsP1
6M
mutant is more sensitive to innate antiviral effectors than RRV T48 in a tissue-specific manner.
In vitro
, we found that the attenuating mutations in nsP1 conferred enhanced sensitivity to type I interferon. In agreement with these findings, RRV T48 and RRV-T48-nsP1
6M
loads were similar in mice deficient in the type I interferon receptor. Our findings suggest that the type I IFN response controls RRV infection in a tissue-specific manner and that specific amino acid changes in nsP1 are determinants of RRV virulence by regulating the sensitivity of RRV to interferon.

IMPORTANCE
Arthritogenic alphaviruses, including Ross River virus (RRV), infect humans and cause debilitating pain and inflammation of the musculoskeletal system. In this study, we identified coding changes in the RRV nsP1 gene that control the virulence of RRV and its sensitivity to the antiviral type I interferon response, a major component of antiviral defense in mammals. Furthermore, our studies revealed that the effects of these attenuating mutations are tissue specific. These findings suggest that these mutations in nsP1 influence the sensitivity of RRV to type I interferon only in specific host tissues. The new knowledge gained from these studies contributes to our understanding of host responses that control alphavirus infection and viral determinants that counteract these responses.
Do health behaviours change after colonoscopy? A prospective cohort study on diet, alcohol, physical activity and smoking among patients and their partners
Authors: Hubbard Gill , Brown Alistair , Campbell Anna , Campbell Neil , Diament Bob , Fielding Shona , Forbat Liz , Masson Lindsey F , O'Carroll Ronan , Stein Kevin , Morrison David S 
Published: January 2014

ObjectivesTo describe diet, alcohol, physical activity and tobacco use prospectively, that is, before and 10 months after colonoscopy for patients and their partners.DesignProspective cohort study of health behaviour change in patients and partners. Comparison groups are patients receiving a normal result notification (NRN) versus patients receiving an abnormal result notification (ARN). Patients and partners (controls) are also compared.Setting5 Scottish hospitals.ParticipantsOf 5798 colonoscopy registrations, 2577 (44%) patients met the eligibility criteria of whom 565 (22%) were recruited; 460 partners were also recruited.MeasuresInternational Physical Activity Questionnaire, Scottish Collaborative Group Food Frequency Questionnaire (includes alcohol), smoking status, sociodemographic characteristics, body mass index, medical conditions, colonoscopy result, Multidimensional Health Locus of Control Scale, behaviour-specific self-efficacy scales.Results57% of patients were men, with a mean age of 60.8 years (SE 0.5) and 43% were from more affluent areas. 72% (n=387) of patients received an ARN and 28% (n=149) received an NRN. Response rate of the second questionnaire was 68.9%. Overall, 27% of patients consumed <5 measures of fruit and vegetables/day, 20% exceeded alcohol limits, 50% had low levels of physical activity and 21% were obese. At 10-month follow-up, a 5% reduction in excessive alcohol consumption and an 8% increase in low levels of physical activity were observed among patients; no significant changes occurred in partners. Baseline high alcohol consumption and low physical activity were the strongest predictors of these behaviours at follow-up. Low alcohol self-efficacy and increasing age were associated with poorer health-related behaviours at follow-up for alcohol consumption and physical activity, respectively.ConclusionsColonoscopy is associated with marginal beneficial changes in some behaviours but not others. Further work is needed to explore how services can optimise increases in beneficial behaviours and mitigate increases in harmful ones.RegistrationsREC REF 10/S0709/24, UKCRN 9911.
Venous thromboembolism: reducing the risk in a Role 3 setting
Authors: Craig Darren G , Adam M G , Proffitt A , Parsons I , Tai N R , d'Arcy J L 
Published: January 2014

BackgroundVenous thromboembolism (VTE) represents a significant preventable cause of hospital mortality. VTE assessment and prophylaxis rates are key patient safety and quality of care indicators. The aim of this study was to audit low molecular weight heparin (LMWH) and graduated elasticated compression stockings (GECS) prescriptions compared with the current Clinical Guidelines for Operations.MethodsComplete audit loop in the Role 3 Hospital, Camp Bastion, Afghanistan. A multifaceted intervention programme incorporating physician and nurse education and pre-printed medication charts was introduced to improve VTE assessment and prophylaxis rates.ResultsOnly 111/301 (36.9%) of patients in the pre-intervention cohort had a VTE risk assessment performed; this improved to 142/155 (91.6%, p<0.0001) post-intervention. A total of 57/88 (64.8%) patients prescribed LMWH pre-intervention had a documented assessment of bleeding risk performed; this rose to 65/66 (98.5%, p=0.0003) post-intervention. In pre-intervention, only 63/213 (29.6%) patients had a documented reassessment of VTE and bleeding risk at 24 h; reassessment rates rose to 68.8% (66/96 patients, p<0.0001) post-intervention. Of those patients at risk of VTE without ongoing bleeding risk, 62/96 (64.6%) had LMWH prescribed pre-intervention; this rose to 57/62 (91.9%) post-intervention (p<0.0001). Inappropriate LMWH prescription rates fell from 26/190 (13.7%) to 4/85 (4.7%, p=0.035) post-intervention. In those patients in whom GECS were not contraindicated, prescription rates rose from 23/95 (24.2%) to 42/62 (67.7%, p<0.0001) post-intervention.ConclusionsInclusion of pre-printed LMWH/GECS prescriptions and risk assessment stickers in the mediction chart significantly improved rates of VTE risk assessment and prophylaxis. These easily reproducible and low-cost interventions could improve patient safety on deployment.
Rational Combination Therapy of Vintafolide (EC145) with Commonly Used Chemotherapeutic Drugs
Authors: Reddy Joseph A. , Dorton Ryan , Bloomfield Alicia , Nelson Melissa , Vetzel Marilynn , Guan John , Leamon Christopher P. 
Published: January 2014

Abstract
Purpose: When evaluated in patients with ovarian and other cancer, vintafolide (EC145), a potent folate-targeted vinca alkaloid conjugate, displayed a toxicity profile that seemed to be nonoverlapping with many standard-of-care cancer therapeutics. It was, therefore, hypothesized that combining vintafolide with certain approved anticancer drugs may afford greater therapeutic efficacy compared with single-agent therapy. To explore this concept, vintafolide was evaluated in combination with pegylated liposomal doxorubicin (PLD; DOXIL), cisplatin, carboplatin, paclitaxel, docetaxel, topotecan, and irinotecan against folate receptor (FR)–positive models.
Experimental Design: FR-expressing KB, M109, IGROV, and L1210 cells were first exposed to graded concentrations of vintafolide, either alone or in combination with doxorubicin (active ingredient in PLD), and isobologram plots and combination index values generated. The vintafolide combinations were also studied in mice bearing various FR-expressing tumors.
Results: Vintafolide displayed strong synergistic activity against KB cells when combined with doxorubicin, and no less-than-additive effects resulted when tested against M109, IGROV, and L1210 cells. In contrast, when either desacetylvinblastine hydrazide (DAVLBH; the vinca alkaloid moiety in vintafolide) or vindesine (the vinca alkaloid most structurally similar to DAVLBH) were tested in combination with doxorubicin, less-than-additive antitumor effects were observed. In vivo, all vintafolide drug combinations produced far greater antitumor effect (complete responses and cures) compared with the single agents alone, without significant increase in overall toxicity. Importantly, these benefits were not observed with combinations of PLD and DAVLBH or vindesine.
Conclusions: On the basis of these encouraging preclinical results, clinical studies to evaluate vintafolide drug combination therapies are now under way. Clin Cancer Res; 20(8); 2104–14. ©2014 AACR.