bluuebunny/crossref_metadata_2025 huggingface dataset:
Sci‐Fri AM: MRI and Diagnostic Imaging ‐ 02: Quality Improvement: Diagnostic Reference Levels for Interior Health CT exams – L‐Spine, Chest/Abdomen/pelvis, Abdomen/Pelvis, Head
Authors: Bjarnason Thorarin
Published: August 2016

Diagnostic Reference Levels are used to optimize patient dose and image quality in the clinical setting. It is assumed that the majority of exams are of diagnostic quality, or the radiologists would request protocol adjustments. By investigating the dose indicator distributions from all scanners, the upper DRL can be set to the 75th percentile of the distribution and a lower DRL can be set to the 10th percentile. Scanners using doses consistently outside the upper/lower DRL range can be adjusted accordingly. 11 CT scanners, all contributing to the American College of Radiology Dose Index Registry (ACR DIR) were used in this study. Dose indicator data were compiled from the ACR DIR data and local DRLs established. Scanners with median doses outside the upper/lower DRL were followed‐up with. Using effective dose and exam volumes, collective dose was determined before and after protocol adjustments to evaluate the effect of this quality improvement effort. The quality initiative is complete for L‐spine and Chest/Abdomen/Pelvis exams and only initial surveys were completed for Head and Abdomen/Pelvis examsg. Median Scanner Dose reductions were 8.8 and 4.9 % for L‐spine and Chest/Abdomen/Pelvis exams, respectively, resulting with collective dose reductions of 0.7 and 3.2 person•Sv/yr. Follow‐up is ongoing for Abdomen/Pelvis and Head exams.
Sci‐Fri AM: MRI and Diagnostic Imaging ‐ 04: How does prostate biopsy guidance error impact pathologic cancer risk assessment?
Authors: Martin Peter , Gaed Mena , Gomez Jose , Moussa Madeleine , Gibson Eli , Cool Derek , Chin Joseph , Pautler Stephen , Fenster Aaron , Ward Aaron
Published: August 2016

Purpose:

MRI‐targeted, 3D transrectal ultrasound (TRUS)‐guided prostate biopsy aims to reduce the 21–47% false negative rate1 of clinical 2D TRUS‐guided sextant biopsy, but still has a substantial false negative rate. This could be improved via biopsy needle target optimization, accounting for uncertainties due to guidance system errors and image registration errors. As an initial step toward this broader goal, we elucidated the impact of biopsy needle delivery error on the probability of obtaining tumour samples and on core involvement. These are both important parameters to patient risk stratification and treatment decision.

Methods:

We investigated this for cancer of all grades, and separately for intermediate/high grade (≥Gleason 4+3) cancer. We used expert‐contoured gold‐standard prostatectomy histology to simulate targeted biopsies using an isotropic Gaussian needle delivery error from 1 to 6 mm, and investigated the amount of cancer obtained in each biopsy core as determined by histology.

Results:

Needle delivery error resulted in core involvement variability that could influence treatment decisions; the presence or absence of cancer in 1/3 or more of each needle core can be attributed to needle delivery error of 4 mm (as observed in practice2).

Conclusions:

Repeated biopsies of the same tumour target can yield percent core involvement measures with sufficient variability to influence the decision between active surveillance and treatment. However, this may be mitigated by making more than one biopsy attempt at selected tumour targets.
Sci‐Fri AM: MRI and Diagnostic Imaging ‐ 05: Comparison of Input Function Measurements from DCE and MOLLI
Authors: Majtenyi Nicholas , Juma Hanif , Klein Ran , deKemp Robert A. , Cron Greg O. , Nguyen Thanh B. , Cameron Ian G.
Published: August 2016

Dynamic contrast‐enhanced (DCE)‐MRI is a technique for obtaining tissue hemodynamic information (e.g. tumours). Despite widespread clinical application of DCE‐MRI, the technique suffers from a lack of standardization and accuracy, especially with respect to the concentration‐versus‐time of gadolinium (Gd) in feeding arteries (the input function, IF). MR phase has a linear quantitative relationship with Gd concentration ([Gd]), making it ideal for measuring the first‐pass of the IF, but is not considered accurate in the steady‐state washout. Modified Look‐Locker Inversion Recovery (MOLLI) is a fast and accurate method to measure T1 and has been validated to quantify typical [Gd] ranges experienced in the washout of the IF.

Two different methods to measure the IF for DCE‐MRI were compared: 1) conventional phase‐versus‐time (“Phase‐only”) and 2) phase‐versus‐time combined with pre‐ and post‐DCE MOLLI T1 measurements (“Phase+MOLLI”). The IF obtained from Phase+MOLLI was calculated from MOLLI T1 values and known relaxivity, then added to the Phase‐only acquisition with the washout IF subtracted. A significant difference was observed between IF values for [Gd] between the Phase‐only and Phase+MOLLI acquisitions (P = 0.03). To ensure the IFs from MOLLI T1s were accurate, it was compared to [Gd] obtained from “gold‐standard” inversion recovery (IR). MOLLI showed excellent agreement with IR when imaged in static phantoms (r2 = 0.997, P = 0.001). The Phase+MOLLI IF was more accurate than the Phase‐only IF in measuring the washout. The Phase+MOLLI acquisition may therefore provide a DCE‐MRI reference standard that could lead to better clinical diagnoses.
Sci‐Fri AM: Quality, Safety, and Professional Issues 01: CPQR Technical Quality Control Suite Development including Quality Control Workload Results
Authors: Malkoske Kyle , Nielsen Michelle , Brown Erika , Diamond Kevin , Frenière Normand , Grant John , Pomerleau‐Dalcourt Natalie , Schella Jason , Schreiner L. John , Tantot Laurent , Barajas Eduardo Villareal , Bissonnette Jean‐Pierre
Published: August 2016

A close partnership between the Canadian Partnership for Quality Radiotherapy (CPQR) and the Canadian Organization of Medical Physicist's (COMP) Quality Assurance and Radiation Safety Advisory Committee (QARSAC) has resulted in the development of a suite of Technical Quality Control (TQC) Guidelines for radiation treatment equipment, that outline specific performance objectives and criteria that equipment should meet in order to assure an acceptable level of radiation treatment quality.

The framework includes consolidation of existing guidelines and/or literature by expert reviewers, structured stages of public review, external field‐testing and ratification by COMP. The adopted framework for the development and maintenance of the TQCs ensures the guidelines incorporate input from the medical physics community during development, measures the workload required to perform the QC tests outlined in each TQC, and remain relevant (i.e. “living documents”) through subsequent planned reviews and updates. This presentation will show the Multi‐Leaf Linear Accelerator document as an example of how feedback and cross‐national work to achieve a robust guidance document.

During field‐testing, each technology was tested at multiple centres in a variety of clinic environments. As part of the defined feedback, workload data was captured. This lead to average time associated with testing as defined in each TQC document. As a result, for a medium‐sized centre comprising 6 linear accelerators and a comprehensive brachytherapy program, we evaluate the physics workload to 1.5 full‐time equivalent physicist per year to complete all QC tests listed in this suite.
Sci‐Fri AM: Quality, Safety, and Professional Issues 04: Predicting waiting times in Radiation Oncology using machine learning
Authors: Joseph Ackeem , Herrera David , Hijal Tarek , Hendren Laurie , Leung Alvin , Wainberg Justin , Sawaf Marya , Maxim Gorshkov , Maglieri Robert , Keshavarz Mehryar , Kildea John
Published: August 2016

We describe a method for predicting waiting times in radiation oncology. Machine learning is a powerful predictive modelling tool that benefits from large, potentially complex, datasets. The essence of machine learning is to predict future outcomes by learning from previous experience. The patient waiting experience remains one of the most vexing challenges facing healthcare. Waiting time uncertainty can cause patients, who are already sick and in pain, to worry about when they will receive the care they need. In radiation oncology, patients typically experience three types of waiting:

Waiting at home for their treatment plan to be prepared

Waiting in the waiting room for daily radiotherapy

Waiting in the waiting room to see a physician in consultation or follow‐up

These waiting periods are difficult for staff to predict and only rough estimates are typically provided, based on personal experience. In the present era of electronic health records, waiting times need not be so uncertain. At our centre, we have incorporated the electronic treatment records of all previously‐treated patients into our machine learning model. We found that the Random Forest Regression model provides the best predictions for daily radiotherapy treatment waiting times (type 2). Using this model, we achieved a median residual (actual minus predicted value) of 0.25 minutes and a standard deviation residual of 6.5 minutes. The main features that generated the best fit model (from most to least significant) are: Allocated time, median past duration, fraction number and the number of treatment fields.
Sci‐Fri AM: Quality, Safety, and Professional Issues 05: QC Program Management and the Benefits of QATrack+
Authors: Angers Crystal Plume , Bottema Ryan , Buckley Lesley , Studinski Ryan
Published: August 2016

Purpose:

Treatment unit uptime statistics are typically used to monitor radiation equipment performance. The Ottawa Hospital Cancer Centre has introduced the use of Quality Control (QC) test success as a quality indicator for equipment performance and overall health of the equipment QC program.

Methods:

Implemented in 2012, QATrack+ is used to record and monitor over 1100 routine machine QC tests each month for 20 treatment and imaging units (http://qatrackplus.com/). Using an SQL (structured query language) script, automated queries of the QATrack+ database are used to generate program metrics such as the number of QC tests executed and the percentage of tests passing, at tolerance or at action. These metrics are compared against machine uptime statistics already reported within the program.

Results:

Program metrics for 2015 show good correlation between pass rate of QC tests and uptime for a given machine. For the nine conventional linacs, the QC test success rate was consistently greater than 97%. The corresponding uptimes for these units are better than 98%. Machines that consistently show higher failure or tolerance rates in the QC tests have lower uptimes. This points to either poor machine performance requiring corrective action or to problems with the QC program.

Conclusions:

QATrack+ significantly improves the organization of QC data but can also aid in overall equipment management. Complimenting machine uptime statistics with QC test metrics provides a more complete picture of overall machine performance and can be used to identify areas of improvement in the machine service and QC programs.
Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 05: A novel respiratory motion simulation program for VMAT treatment plans: a phantom validation study
Authors: Hubley Emily , Pierce Greg , Ploquin Nicolas
Published: August 2016

Purpose:

To develop and validate a computational method to simulate craniocaudal respiratory motion in a VMAT treatment plan.

Methods:

Three 4DCTs of the QUASAR respiratory motion phantom were acquired with a 2cm water‐density spherical tumour embedded in cedar to simulate lung. The phantom was oscillating sinusoidally with an amplitude of 2cm and periods of 3, 4, and 5 seconds. An ITV was contoured and 5mm PTV margin was added. High and a low modulation factor VMAT plans were created for each scan. An in‐house program was developed to simulate respiratory motion in the treatment plans by shifting the MLC leaf positions relative to the phantom. Each plan was delivered to the phantom and the dose was measured using Gafchromic film. The measured and calculated plans were compared using an absolute dose gamma analysis (3%/3mm).

Results:

The average gamma pass rate for the low modulation plan and high modulation plans were 91.1% and 51.4% respectively. The difference between the high and low modulation plans gamma pass rates is likely related to the different sampling frequency of the respiratory curve and the higher MLC leaf speeds in the high modulation plan. A high modulation plan has a slower gantry speed and therefore samples the breathing cycle at a coarser frequency leading to inaccuracies between the measured and planned doses.

Conclusion:

A simple program, including a novel method for increasing sampling frequency beyond the control point frequency, has been developed to simulate respiratory motion in VMAT plans by shifting the MLC leaf positions.
Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 07: Transitioning from extended‐distance total body irradiation to optimized VMAT total marrow irradiation
Authors: Cherpak Amanda , Chytyk‐Praznik Krista , Yewondwossen Mammo , Schella Jason , Davis Carol‐Anne , Day Allan , DeGiobbi Jennifer , McAloney Dave , Mulroy Liam
Published: August 2016

Purpose:

TMI targets only the bone marrow, with the intent of sparing normal tissues. The NSCC has recently implemented a TMI protocol which includes VMAT fields to treat the bone marrow from head to mid‐thigh and extended SSD POP fields to treat the lower legs. This work describes the commissioning and initial clinical results of the first reported VMAT TMI treatments in Canada.

Methods:

Detailed CT simulation, imaging, planning and treatment procedures were developed by a multi‐disciplinary team. Patients have 1 cm of bolus over the lower legs and 0.5 cm of bolus around the lower arms. The PTV includes all bone, except mandible, facial bones and hands, with the objective of V(12 Gy) > 90%. Detailed analysis of the influence of field overlap was performed to determine optimal field placement and image‐guidance tolerances.

Results:

PTV coverage was achieved for all cases as V(12 Gy) ranged from 90.4–96.3%. The minimum dose to the PTV, D(99%), ranged from 91.4–97.87% and V(90%Rx=10.8 Gy) ranged from 99.1–100.0%. The lungs, liver and heart had an average Dmean of (7.8±0.3)Gy/(65±2)%, (7.6±0.7)Gy/(63±5)%, and (6.8±0.4)Gy/(56±4)% respectively.

Conclusions:

Commissioning required input and collaboration from all team members. Transitioning from TBI to TMI requires additional time for contouring, treatment planning, QA, and treatment. Patient benefit can however be seen in the quality of OAR sparing.
Sci‐Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques ‐ 10: Results from Canada Wide Survey on Total Body Irradiation Practice
Authors: Studinski Ryan , Fraser Danielle , Samant Rajiv , MacPherson Miller
Published: August 2016

Purpose:

Total Body Irradiation (TBI) is delivered to a relatively small number of patients with a variety of techniques; it has been a challenge to develop consensus studies for best practice. This survey was created to assess the current state of TBI in Canada.

Methods:

The survey was created with questions focusing on the radiation prescription, delivery technique and resources involved. The survey was circulated electronically to the heads of every clinical medical physics department in Canada. Responses were gathered and collated, and centres that were known to deliver TBI were urged to respond.

Results:

Responses from 20 centres were received, including 12 from centres that perform TBI. Although a variety of TBI dose prescriptions were reported, 12 Gy in 6 fractions was used in 11 centres while 5 centres use unique prescriptions. For dose rate, a range of 9 to 51 cGy/min was reported.

Most centres use an extended SSD technique, with the patient standing or lying down against a wall. The rest use either a “sweeping” technique or a more complicated multi‐field technique. All centres but one indicated that they shield the lungs, and only a minority shield other organs.

The survey also showed that considerable resources are used for TBI including extra staffing, extended planning and treatment times and the use of locally developed hardware or software.

Conclusions:

This survey highlights that both similarities and important discrepancies exist between TBI techniques across the country, and is an opportunity to prompt more collaboration between centres.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 03: Energy dependence of a clinical probe‐format calorimeter and its pertinence to absolute photon and electron beam dosimetry
Authors: Renaud James , Seuntjens Jan , Sarfehnia Arman
Published: August 2016

Purpose:

To evaluate the intrinsic and absorbed‐dose energy dependence of a small‐scale graphite calorimeter probe (GPC) developed for use as a routine clinical dosimeter. The influence of charge deposition on the response of the GPC was also assessed by performing absolute dosimetry in clinical linac‐based electron beams.

Methods:

Intrinsic energy dependence was determined by performing constant‐temperature calorimetry dose measurements in a water‐equivalent solid phantom, under otherwise reference conditions, in five high‐energy photon (63.5 < %dd(10)X < 76.3), and five electron (2.3 cm < R50 < 8.3 cm) beams. Reference dosimetry was performed for all beams in question using an Exradin A19 ion chamber with a calibration traceable to national standards. The absorbed‐dose component of the overall energy dependence was calculated using the EGSnrc egs_chamber user code.

Results:

A total of 72 measurements were performed with the GPC, resulting in a standard error on the mean absorbed dose of better than 0.3 % for all ten beams. For both the photon and electron beams, no statistically‐significant energy dependence was observed experimentally. Peak‐to‐peak, variations in the relative response of the GPC across all beam qualities of a given radiation type were on the order of 1 %. No effects, either transient or permanent, were attributable to the charge deposited by the electron beams.

Conclusions:

The GPC's apparent energy‐independence, combined with its well‐established linearity and dose rate independence, make it a potentially useful dosimetry system capable measuring photon and electron doses in absolute terms at the clinical level.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 06: Investigation of an absorbed dose to water formalism for a miniature low‐energy x‐ray source
Authors: Watson Peter , Seuntjens Jan
Published: August 2016

Purpose:

We present a formalism for calculating the absorbed dose to water from a miniature x‐ray source (The INTRABEAM system, Carl Zeiss), using a parallel‐plate ionization chamber calibrated in terms of air‐kerma. Monte Carlo calculations were performed to derive a chamber conversion factor (CQ) from reference air‐kerma to dose to water for the INTRABEAM. CQ was investigated as a function of depth in water, and compared with the manufacturer's reported value. The effect of chamber air cavity dimension tolerance was also investigated.

Methods:

Air‐kerma (Ak) from a reference beam was calculated using the EGSnrc user code cavity. Using egs_chamber, a model of a PTW 34013 parallel‐plate ionization chamber was created according to manufacturer specifications. The dose to the chamber air cavity (Dgas) was simulated both in‐air (with reference beam) and in‐water (with INTRABEAM source). Dose to a small water voxel (Dw) was also calculated. CQ was derived from these quantities.

Results:

CQ was found to vary by up to 15% (1.30 vs 1.11) between chamber dimension extremes. The agreement between chamber CQ was found to improve with increasing depth in water. However, in all cases investigated, CQ was larger than the manufacturer reported value of 1.054.

Conclusions:

Our results show that cavity dimension tolerance has a significant effect on CQ, with differences as large as 15%. In all cases considered, CQ was found to be larger than the reported value of 1.054. This suggests that the recommended calculation underestimates the dose to water.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 08: A Low‐Cost Optical Scanner and Gantry for use with 3D Printing of Radiation Therapy Accessories
Authors: Rickey Daniel , Sasaki David , Dubey Arbind , Harris Chad , Johnson Kate , Egtberts Andy , Koul Rashmi
Published: August 2016

Purpose:

Three‐dimensional printing has been implemented at our institution to create customized treatment accessories including shielding and bolus. In order to effectively use 3D printing, the topography of the patient must first be acquired. To this end, we have evaluated a low‐cost structured‐light 3D scanner in order to assess the clinical viability of this technology.

Methods:

For ease of use, the scanner (3D Systems, Sense 3D Scanner) was mounted in a simple gantry that guided its motion and maintained an optimum distance between the scanner and the object. To characterise the spatial accuracy of the scanner, we used a geometric phantom and an anthropomorphic head phantom. The geometric phantom was machined from plastic and had overall dimensions of 24 cm by 15 cm and included a hemispherical and a tetrahedron protrusion roughly the dimensions of an average forehead and nose respectively. Meshes acquired by the optical scanner were compared to meshes generated from high‐resolution CT images.

Results:

Scans were acquired in under one minute. Most of the optical scans contained noticeable artefacts although in most instances these were considered minor. Using an algorithm that calculated distances between the two meshes, we found most of the optical scanner measurements agreed with those from CT to within about 1 mm for the geometric phantom and to within about 2 mm for the head phantom.

Conclusion:

In summary, we deemed this scanner to be clinically acceptable and it has been used to design treatment accessories for several skin cancer patients.
Sci‐Sat AM: Radiation Dosimetry and Practical Therapy Solutions ‐ 10: Towards LET detection: A study on the effects of scintillator doping
Authors: Nusrat Humza , Pang Geordi , Ahmad Syed , Keller Brian , Sarfehnia Arman
Published: August 2016

Purpose:

In radiotherapy, the amount of radiation delivered is determined by optimizing the amount of absorbed dose to the tumor. Dose does not always correlate well with the actual biological effects of radiation. This work seeks to validate the LET‐dependence of doped plastic scintillators for use in a radiation beam quality (LET) detector.

Methods:

The LET spectrum ([Φ]) can be resolved knowing the measured signals of uniquely LET‐dependent detectors, [S], and the response of each LET‐dependent detector to specific LETs ([R]), through the relation [Φ]=[S][R]−1. Plastic scintillator response is intrinsically LET dependent and can be varied via doping. Initial prototype consists of plastic scintillator and glass taper coupled to an optical fiber; components are housed in black acrylic, reducing effect of ambient light. In order to determine [R], the light response matrix, GEANT4.10.1 Monte Carlo (MC) was used. To validate MC, measurements were done using high energy electrons (9,12,15MeV) and orthovoltage x‐rays (100,250kV); scintillator signal was normalized to dose measured simultaneously.

Results:

Stopping power was varied by changing particle type/energy; measurements indicated that as stopping power increased from 1.9 to 6.6MeV/cm, detector response increased by 263% (+/−29.2%) for 5%Pb‐doped scintillator (155% in MC); 52% (+/−7.8%) increase observed when undoped scintillator was used (49% in MC). 5%Pb‐doped discrepancy (100kV x‐rays) is being investigated.

Conclusions:

This work validates that doping effects LET/energy response of scintillators; an effect that can be utilized for construction of an LET detector.
Let’s Weigh in on “Deflategate”
Authors: Toepker Terrence
Published: August 2016

The September 2015 paper “Bouncing Back from ‘Deflategate’” is a very interesting article from a physics viewpoint. However, we doubt that the National Football League (NFL) officials will bounce footballs and measure the coefficient of restitution to verify that the footballs remain properly inflated. The release of a few pounds per square inch (psi) from a football seems trivial until one reads about the millions of dollars in suspensions, fines, and legal fees that were accrued. What is a possible solution that the NFL might actually use? Weigh the ball! When a small amount of air is deliberately released, causing a change in pressure, the change in mass can be calculated and measured. Note that the change in mass can be measured without making another pressure measurement. This is important because the reinsertion of the needle of the gauge to make another measurement causes a small inadvertent loss of pressure and mass from the ball.
Single-Slit Diffraction: Transitioning from Geometric Optics to the Fraunhofer Regime
Authors: Panuski Christopher L. , Mungan Carl E.
Published: August 2016

Suppose a red laser beam (of wavelength λ equal to 0.660 μm) is expanded using an optical telescope into a collimated, approximately plane wave that is 5.68 mm in diameter. Pass that beam through a tall rectangular slit whose width a is gradually reduced from 3.30 to 0.100 mm. Look at its image on a screen located at a distance L from the slit equal to 0.656 m. As the slit is narrowed, you predict that the width of the pattern will: smoothly increase,smoothly decrease,increase and then decrease, ordecrease and then increase.
Relationships Among Middle School Students’ Expectancy Beliefs, Task Values, and Health-Related Fitness Performance
Authors: Chen Han , Sun Haichun , Dai Jun , Griffin Michael
Published: August 2016

Purpose:

The purpose of the study was to identify gender and body weight differences in Chinese adolescents’ perceived expectancy value (EV) motivation in their physical education (PE) class. The study also explored the relationship between EV and adolescents’ health-related fitness performances.

Method:

A group of seventh and eighth graders (N = 224) from China were measured on EV toward PE as well as health-related fitness levels. A two-way MANOVA test was used to examine gender and body weight differences in EV motivations. Several two-step hierarchical multiple regression analyses were conducted to examine the relationship between EV motivation and various fitness performances while controlling for the effects of gender and body weight.

Results:

Boys had higher expectancy beliefs and perceived their PE class as more interesting, useful, and important than girls did. Compared with overweight/obese students, students in the healthy weight group reported higher expectancy beliefs. When the effects of gender and body weight were accounted for, expectancy beliefs were the only reliable predictor influencing adolescents’ cardiorespiratory as well as muscular strength/endurance fitness levels.

Discussion/Conclusion:

Physical educators should use various teaching strategies to enhance students’ expectancy beliefs and task values. This is especially important for female students and overweight/obese students.
Chemists to get preprint server of their own
Authors: Voosen Paul
Published: August 2016

American Chemical Society launches ChemRxiv despite dubious precedents.
Prenatal acoustic communication programs offspring for high posthatching temperatures in a songbird
Authors: Mariette Mylene M. , Buchanan Katherine L.
Published: August 2016

In many species, embryos can perceive and learn external sounds. Yet, the possibility that parents may use these embryonic capacities to alter their offspring’s developmental trajectories has not been considered. Here, we demonstrate that zebra finch parents acoustically signal high ambient temperatures (above 26°C) to their embryos. We show that exposure of embryos to these acoustic cues alone adaptively alters subsequent nestling begging and growth in response to nest temperature and influences individuals’ reproductive success and thermal preferences as adults. These findings have implications for our understanding of maternal effects, phenotypic plasticity, developmental programming, and the adaptation of endothermic species to a warming world.
The quest to burn fat, effortlessly and safely
Authors: Fan Weiwei , Evans Ronald
Published: August 2016

An enzyme steps up to BAT as a potential mitochondrial uncoupler
Multicenter Evaluation of BD Max Enteric Parasite Real-Time PCR Assay for Detection of Giardia duodenalis, Cryptosporidium hominis, Cryptosporidium parvum, and Entamoeba histolytica
Authors: Madison-Antenucci S. , Relich R. F. , Doyle L. , Espina N. , Fuller D. , Karchmer T. , Lainesse A. , Mortensen J. E. , Pancholi P. , Veros W. , Harrington S. M.
Published: August 2016

Common causes of chronic diarrhea among travelers worldwide include protozoan parasites. The majority of parasitic infections are caused by
Giardia duodenalis
,
Entamoeba histolytica
,
Cryptosporidium parvum
, and
Cryptosporidium hominis
. Similarly, these species cause the majority of parasitic diarrhea acquired in the United States. Detection of parasites by gold standard microscopic methods is time-consuming and requires considerable expertise; enzyme immunoassays and direct fluorescent-antibody (DFA) stains have lowered hands-on time for testing, but improvements in sensitivity and technical time may be possible with a PCR assay. We performed a clinical evaluation of a multiplex PCR panel, the enteric parasite panel (EPP), for the detection of these common parasites using the BD Max instrument, which performs automated extraction and amplification. A total of 2,495 compliant specimens were enrolled, including 2,104 (84%) specimens collected prospectively and 391 (16%) specimens collected retrospectively. Approximately equal numbers were received in 10% formalin (1,273 specimens) and unpreserved (1,222 specimens). The results from the EPP were compared to those from alternate PCR and bidirectional sequencing (APCR), as well as DFA (
G. duodenalis
and
C. parvum
or
C. hominis
) or trichrome stain (
E. histolytica
). The sensitivity and specificity for prospective and retrospective specimens combined were 98.2% and 99.5% for
G. duodenalis
, 95.5% and 99.6 for
C. parvum
or
C. hominis
, and 100% and 100% for
E. histolytica
, respectively. The performance of the FDA-approved BD Max EPP compared well to the reference methods and may be an appropriate substitute for microscopic examination or immunoassays.
Commentary: The Confounding Role of Antimicrobial Stewardship Programs in Understanding the Impact of Technology on Patient Care
Authors: Doern Christopher D.
Published: August 2016

Numerous studies have demonstrated the benefit of the combination of antimicrobial stewardship program (ASP) intervention and rapid diagnostic testing (RDT). However, few studies have attempted to study the incremental benefit of ASP and RDT, making it difficult to understand the true benefits of each intervention. This issue is discussed in the context of an article by S. H. McVane and F. S. Nolte (J Clin Microbiol 54:2476–2484, 2016,
http://dx.doi.org/doi:10.1128/JCM.00996-16
), with suggestions about how the findings of this study can be applied to other areas of clinical microbiology.
High Glucose Induces Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus
Authors: Ye Fengchun , Zeng Yan , Sha Jingfeng , Jones Tiffany , Kuhne Kurt , Wood Charles , Gao Shou-Jiang
Published: August 2016

A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute to KS development. We found elevated levels of viral lytic gene expression when Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells were cultured in high-glucose medium. To demonstrate the association between high glucose levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose levels induced the production of hydrogen peroxide (H
2
O
2
), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection.

IMPORTANCE
Multiple epidemiological studies have reported a higher prevalence of classic KS in diabetic patients. By using both
in vitro
and
in vivo
models, we demonstrated an association between high glucose levels and KSHV lytic replication. High glucose levels induce oxidative stress and the production of H
2
O
2
, which mediates the reactivation of latent KSHV through multiple mechanisms. Our results provide the first experimental evidence and mechanistic support for the association of classic KS with diabetes.
Lineage-Specific Differences between the gp120 Inner Domain Layer 3 of Human Immunodeficiency Virus and That of Simian Immunodeficiency Virus
Authors: Ding Shilei , Medjahed Halima , Prévost Jérémie , Coutu Mathieu , Xiang Shi-Hua , Finzi Andrés
Published: August 2016

Binding of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to layer 1 of HIV-1 gp120, the SIVmac239 gp120 layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved tryptophan at position 375 (Trp 375) in HIV-2/SIVsmm. In this study, we investigated the role of SIV layer 3 in viral entry, cell-to-cell fusion, and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity, which directly contacts CD4. In summary, our results suggest that layer 3 in SIV has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in layer 3 from HIV-1 and that from SIV.

IMPORTANCE
CD4-induced conformational changes in the gp120 inner domain involve rearrangements between three topological layers. While the role of layers 1 to 3 for HIV-1 and layers 1 and 2 for SIV on gp120 transition to the CD4-bound conformation has been reported, the role of SIV layer 3 remains unknown. Here we report that SIV layer 3 has a greater impact on CD4 binding than does layer 3 in HIV-1 gp120. This work defines lineage-specific differences in layer 3 from HIV-1 and SIV.
Inhibition of Polyamine Biosynthesis Is a Broad-Spectrum Strategy against RNA Viruses
Authors: Mounce Bryan C. , Cesaro Teresa , Moratorio Gonzalo , Hooikaas Peter Jan , Yakovleva Anna , Werneke Scott W. , Smith Everett Clinton , Poirier Enzo Z. , Simon-Loriere Etienne , Prot Matthieu , Tamietti Carole , Vitry Sandrine , Volle Romain , Khou Cécile , Frenkiel Marie-Pascale , Sakuntabhai Anavaj , Delpeyroux Francis , Pardigon Nathalie , Flamand Marie , Barba-Spaeth Giovanna , Lafon Monique , Denison Mark R. , Albert Matthew L. , Vignuzzi Marco
Published: August 2016

RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise
in vitro
and
in vivo
, these outbreaks underscore the need to accelerate drug discovery. The replication of several viruses has been described to rely on host polyamines, small and abundant positively charged molecules found in the cell. Here, we describe the antiviral effects of two molecules that alter polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhibitor of ornithine decarboxylase 1 (ODC1), and diethylnorspermine (DENSpm), an activator of spermidine/spermine
N
1
-acetyltransferase (SAT1). We show that reducing polyamine levels has a negative effect on diverse RNA viruses, including several viruses involved in recent outbreaks,
in vitro
and
in vivo
. These findings highlight the importance of the polyamine biosynthetic pathway to viral replication, as well as its potential as a target in the development of further antivirals or currently available molecules, such as DFMO.

IMPORTANCE
RNA viruses present a significant hazard to human health, and combatting these viruses requires the exploration of new avenues for targeting viral replication. Polyamines, small positively charged molecules within the cell, have been demonstrated to facilitate infection for a few different viruses. Our study demonstrates that diverse RNA viruses rely on the polyamine pathway for replication and highlights polyamine biosynthesis as a promising drug target.
Evidence for the Introduction, Reassortment, and Persistence of Diverse Influenza A Viruses in Antarctica
Authors: Hurt Aeron C. , Su Yvonne C. F. , Aban Malet , Peck Heidi , Lau Hilda , Baas Chantal , Deng Yi-Mo , Spirason Natalie , Ellström Patrik , Hernandez Jorge , Olsen Bjorn , Barr Ian G. , Vijaykrishna Dhanasekaran , Gonzalez-Acuna Daniel
Published: August 2016

Avian influenza virus (AIV) surveillance in Antarctica during 2013 revealed the prevalence of evolutionarily distinct influenza viruses of the H11N2 subtype in Adélie penguins. Here we present results from the continued surveillance of AIV on the Antarctic Peninsula during 2014 and 2015. In addition to the continued detection of H11 subtype viruses in a snowy sheathbill during 2014, we isolated a novel H5N5 subtype virus from a chinstrap penguin during 2015. Gene sequencing and phylogenetic analysis revealed that the H11 virus detected in 2014 had a >99.1% nucleotide similarity to the H11N2 viruses isolated in 2013, suggesting the continued prevalence of this virus in Antarctica over multiple years. However, phylogenetic analysis of the H5N5 virus showed that the genome segments were recently introduced to the continent, except for the NP gene, which was similar to that in the endemic H11N2 viruses. Our analysis indicates geographically diverse origins for the H5N5 virus genes, with the majority of its genome segments derived from North American lineage viruses but the neuraminidase gene derived from a Eurasian lineage virus. In summary, we show the persistence of AIV lineages in Antarctica over multiple years, the recent introduction of gene segments from diverse regions, and reassortment between different AIV lineages in Antarctica, which together significantly increase our understanding of AIV ecology in this fragile and pristine environment.

IMPORTANCE
Analysis of avian influenza viruses (AIVs) detected in Antarctica reveals both the relatively recent introduction of an H5N5 AIV, predominantly of North American-like origin, and the persistence of an evolutionarily divergent H11 AIV. These data demonstrate that the flow of viruses from North America may be more common than initially thought and that, once introduced, these AIVs have the potential to be maintained within Antarctica. The future introduction of AIVs from North America into the Antarctic Peninsula is of particular concern given that highly pathogenic H5Nx viruses have recently been circulating among wild birds in parts of Canada and the Unites States following the movement of these viruses from Eurasia via migratory birds. The introduction of a highly pathogenic influenza virus in penguin colonies within Antarctica might have devastating consequences.
A conceptual and practical approach to haemostasis in paediatric liver disease
Authors: Magnusson Maria , Ignjatovic Vera , Hardikar Winita , Monagle Paul
Published: August 2016

Children with liver disease can develop severe bleeding episodes and thrombosis. Liver failure usually results in decreased levels of procoagulant and anticoagulant factors. Additional risk factors, including changes in vascular flow and endothelial function, are of importance for the development of bleeding or thrombosis in individual vascular beds. Detailed studies of haemostatic disturbances in the setting of paediatric liver disease are sparse and extrapolation from adult studies is common. The spectrum of liver diseases and the haemostatic system differs between children and adults. Specific paediatric liver diseases are reported to have more distinctive effects on haemostasis and the risk of bleeding and/or thrombosis. Conclusion: we propose a model regarding haemostasis in paediatric liver disease, taking into account a number of specific variables and mechanisms, as well as the type of liver disease, which will provide a framework for clinical decision-making in these complex patients.
ASSESSMENT OF VANCOMYCIN CONCENTRATIONS IN SYRINGES PREPARED WITHIN A WARD SETTING
Authors: Saimbi Sarina , Batchelor Hannah , Whitticase Louise , Holder Gemma , Russell Alison Bedford
Published: August 2016

Aim

Vancomycin is used as a second line antibiotic in the treatment of late onset neonatal infection for its activity against coagulase negative staphylococci. Vancomycin infusions are prepared within a ward setting for administration to neonates. Differences in preparation techniques on the ward have previously been recognised as a potential source of variation in vancomycin concentrations, as compared to concentrations in pre-made preparations. This study analyses a consecutive series of vancomycin syringes prepared in a ward for administration to neonates, to determine how accurate the concentration of each preparation was compared to the expected concentration.

Method

Vancomycin concentrations were determined by UV analysis (λ=280 nm) with a UV spectrophotometer (Jenway Genova Plus). A calibration curve for vancomycin was created (R2=0.9996) by manufacturing a series of solutions of vancomycin hydrochloride in glucose 5% w/v.

Samples of vancomycin from syringes from which doses were administered to neonates were then analysed to assess their concentration. For each syringe, mean vancomycin concentration±standard deviation was calculated (n=3).

Reasonable errors in preparations were calculated based on errors in each step of the preparation process. Theoretical error was calculated based on apparatus used, and experimental error was recorded based on a simulated process. Two preparation methods were compared; the method complying with that described in the local formulary, 1 and an alternative method reported by the nurses preparing the dose.

Results

Analysis of results showed that concentration of the vancomycin syringes prepared ranged from 0.85 to 8.24 mg/mL. The expected concentration was 4.17 mg/ml.

Theoretical error in preparation of vancomycin doses was lower with the formulary-compliant method1 versus an alternative method, as were variations in in vancomycin concentration.

Depending on the type of error (theoretical or experimental) and method by which vancomycin syringes were prepared (formulary1 or alternative method), the percentage of syringes with vancomycin concentration outside of the specified ranges varied from 20%–43%. This is higher compared to the findings of the Department of Health2, where it was found that 19.2% of morphine infusions prepared by nurses in the neonatal intensive care unit were outside British Pharmacopoeia concentration limits.

Conclusion

Preparation of vancomycin doses should follow the formulary method1 to minimise variation in concentration of the final product. Alternatively, pre-made syringes may be preferred as an alternative to ward-made syringes as this removes individualised preparation as a source of error.
A STABILITY STUDY OF OMEPRAZOLE DILUTED IN SODIUM CHLORIDE FOR INTRAVENOUS INFUSION AND DISCUSSION REGARDING CURRENT PRACTICE IN UK PAEDIATRIC INTENSIVE CARE UNITS
Authors: Morris Stephen , Ellard Olivia
Published: August 2016

Background

Omeprazole by intravenous infusion is occasionally warranted in children during episodes of acute upper gastrointestinal bleeding. This is to ensure the continued suppression of stomach acid to reduce the of risk of rebleeding.

Methods

Current practice in UK paediatric intensive care units varies, but the use of 160 mg/1.73 m3 over 24 hours has previously been reported.1 This is commonly prepared as a 0.8 mg/ml solution changed either at 12 or 24 hrs after preparation depending on reference source used.2-3 The current practice of using a 0.8 mg/ml (40 mg/50 ml) is off label and not endorsed by manufacturers who recommend a maximum concentration of 0.4 mg/ml3.

Following these recommendations would lead to a fluid load of 400 ml/1.73 m2 which is likely to be significant. Excess fluid intake has been shown to correlate with increased oxygenation index and increased PICU stay.4

The aim of this study is to provide stability data for using 0.8 mg/ml for intravenous infusion which is currently in wide spread despite use a lack of published lack of data in this area.

Methods

A series of analytical techniques were performed to assess physical and chemical stability. Test solutions were pre pared by reconstituting Losec® (Omeprazole) 40 mg powder for infusion and diluting to either 50 ml or 100 ml in 0.9% sodium chloride.

Reverse phase HPLC analysis was conducted at 0 hrs, 10 hrs and 24 hrs. Particle size was assessed using a zeta potential analyser at 15-minute intervals over 60 minutes.

Results

At both 40 mg/50 mL and 40 mg/100 mL the concentration of omeprazole remained at 101% and 100% after 10 hours respectively. However, significant degradation was seen at 24 hours as concentrations reduced to 60% and 55% respectively.