bluuebunny/crossref_metadata_2025 huggingface dataset:
A software tool to automatically assure and report daily treatment deliveries by a cobalt‐60 radiation therapy device
Authors: Yang Deshan , Wooten H. Omar , Green Olga , Li Harold H. , Liu Shi , Li Xiaoling , Rodriguez Vivian , Mutic Sasa , Kashani Rojano
Published: February 2017

The aims of this study were to develop a method for automatic and immediate verification of treatment delivery after each treatment fraction in order to detect and correct errors, and to develop a comprehensive daily report which includes delivery verification results, daily image‐guided radiation therapy (IGRT) review, and information for weekly physics reviews. After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a commercial MRI‐guided radiotherapy treatment machine, we designed a procedure to use 1) treatment plan files, 2) delivery log files, and 3) beam output information to verify the accuracy and completeness of each daily treatment delivery. The procedure verifies the correctness of delivered treatment plan parameters including beams, beam segments and, for each segment, the beam‐on time and MLC leaf positions. For each beam, composite primary fluence maps are calculated from the MLC leaf positions and segment beam‐on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. A daily treatment delivery report is designed to include all required information for IGRT and weekly physics reviews including the plan and treatment fraction information, daily beam output information, and the treatment delivery verification results. A computer program was developed to implement the proposed procedure of the automatic delivery verification and daily report generation for an MRI guided radiation therapy system. The program was clinically commissioned. Sensitivity was measured with simulated errors. The final version has been integrated into the commercial version of the treatment delivery system. The method automatically verifies the EBRT treatment deliveries and generates the daily treatment reports. Already in clinical use for over one year, it is useful to facilitate delivery error detection, and to expedite physician daily IGRT review and physicist weekly chart review.

PACS number(s): 87.55.km
Addendum to brachytherapy dose‐volume histogram commissioning with multiple planning systems
Authors: Gossman Michael S.
Published: February 2017

The process for validating dose‐volume histogram data in brachytherapy software is presented as a supplement to a previously published article. Included is the DVH accuracy evaluation of the Best NOMOS treatment planning system called “Best TPS VohvmePlan” As done previously in other software, a rectangular cuboid was contoured in the treatment planning system. A single radioactive 125I source was positioned coplanar and concentric with one end. Calculations were performed to estimate dose deposition in partial volumes of the cuboid structure, using the brachytherapy dosimetry formalism defined in AAPM Task Group 43. Hand‐calculated, dose‐volume results were compared to TPS‐generated, point‐source‐approximated dose‐volume histogram data to establish acceptance. The required QA for commissioning was satisfied for the DVH as conducted previously for other software, using the criterion that the DVH “actual variance” calculations should differ by no more than 5% at any specific radial distance with respect to , and the “average variance” DVH calculations should differ by no more than 2% over all radial distances with respect to . The average disagreement observed between hand calculations and treatment planning system DVH was less than 0.5% on average for this treatment planning system and less than 1.1% maximally for .

PACS number(s): 87.10.+e, 87.55.‐x, 87.53.Jw, 07.05.Tp
Inverse treatment planning for spinal robotic radiosurgery: an international multi‐institutional benchmark trial
Authors: Blanck Oliver , Wang Lei , Baus Wolfgang , Grimm Jimm , Lacornerie Thomas , Nilsson Joakim , Luchkovskyi Sergii , Cano Isabel Palazon , Shou Zhenyu , Ayadi Myriam , Treuer Harald , Viard Romain , Siebert Frank‐Andre , Chan Mark K.H. , Hildebrandt Guido , Dunst Jürgen , Imhoff Detlef , Wurster Stefan , Wolff Robert , Romanelli Pantaleo , Lartigau Eric , Semrau Robert , Soltys Scott G. , Schweikard Achim
Published: February 2017

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high‐dose radiation to well‐defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user‐dependent. We performed an international, multi‐institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex‐shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (, ) and target (coverage ). The resulting plans were rated on a scale from 1 to 4 (excellent‐poor) in five categories (constraint compliance, optimization goals, low‐dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathematically rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2‐4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well‐balanced trade‐off among all planning objectives was preferred for treatment by most participants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi‐institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

PACS number(s): 87.55.de
On flattening filter‐free portal dosimetry
Authors: Pardo Eduardo , Novais Juan Castro , Molina López María Yolanda , Maqueda Sheila Ruiz
Published: February 2017

Varian introduced (in 2010) the option of removing the flattening filter (FF) in their C‐Arm linacs for intensity‐modulated treatments. This mode, called flattening filter‐free (FFF), offers the advantage of a greater dose rate. Varian's “Portal Dosimetry” is an electronic portal imager device (EPID)‐based tool for IMRT verification. This tool lacks the capability of verifying flattening filter‐free (FFF) modes due to saturation and lack of an image prediction algorithm. (Note: the latest versions of this software and EPID correct these issues.) The objective of the present study is to research the feasibility of said verifications (with the older versions of the software and EPID). By placing the EPID at a greater distance, the images can be acquired without saturation, yielding a linearity similar to the flattened mode. For the image prediction, a method was optimized based on the clinically used algorithm (analytical anisotropic algorithm (AAA)) over a homogeneous phantom. The depth inside the phantom and its electronic density were tailored. An application was developed to allow the conversion of a dose plane (in DICOM format) to Varian's custom format for Portal Dosimetry. The proposed method was used for the verification of test and clinical fields for the three qualities used in our institution for IMRT: 6X, 6FFF and 10FFF. The method developed yielded a positive verification (more than 95% of the points pass a gamma) for both the clinical and test fields. This method was also capable of “predicting” static and wedged fields. A workflow for the verification of FFF fields was developed. This method relies on the clinical algorithm used for dose calculation and is able to verify the FFF modes, as well as being useful for machine quality assurance. The procedure described does not require new hardware. This method could be used as a verification of Varian's Portal Dose Image Prediction.

PACS number(s): 87.53.Kn, 87.55.T‐, 87.56.bd, 87.59.‐e
Automated Calculation of Water‐equivalent Diameter (DW) Based on AAPM Task Group 220
Authors: Anam Choirul , Haryanto Freddy , Widita Rena , Arif Idam , Dougherty Geoff
Published: February 2017

The purpose of this study is to accurately and effectively automate the calculation of the water‐equivalent diameter () from 3D CT images for estimating the size‐specific dose. is the metric that characterizes the patient size and attenuation. In this study, was calculated for standard CTDI phantoms and patient images. Two types of phantom were used, one representing the head with a diameter of 16 cm and the other representing the body with a diameter of 32 cm. Images of 63 patients were also taken, 32 who had undergone a CT head examination and 31 who had undergone a CT thorax examination. There are three main parts to our algorithm for automated calculation. The first part is to read 3D images and convert the CT data into Hounsfield units (HU). The second part is to find the contour of the phantoms or patients automatically. And the third part is to automate the calculation of based on the automated contouring for every slice (). The results of this study show that the automated calculation of and the manual calculation are in good agreement for phantoms and patients. The differences between the automated calculation of and the manual calculation are less than 0.5%. The results of this study also show that the estimating of using (central slice along longitudinal axis) produces percentage differences of and , and estimating using produces percentage differences of and , for thorax and head examinations, respectively. From this study, the percentage differences between normalized size‐specific dose estimate for every slice () and are and for thorax and head examinations, respectively; between and are and for thorax and head examinations, respectively.

PACS number(s): 87.57.Q‐, 87.57.uq‐
Evaluation of target and cardiac position during visually monitored deep inspiration breath‐hold for breast radiotherapy
Authors: Conroy Leigh , Yeung Rosanna , Watt Elizabeth , Quirk Sarah , Long Karen , Hudson Alana , Phan Tien , Smith Wendy L.
Published: February 2017

A low‐resource visually monitored deep inspiration breath‐hold (VM‐DIBH) technique was successfully implemented in our clinic to reduce cardiac dose in left‐sided breast radiotherapy. In this study, we retrospectively characterized the chest wall and heart positioning accuracy of VM‐DIBH using cine portal images from 42 patients. Central chest wall position from field edge and in‐field maximum heart distance (MHD) were manually measured on cine images and compared to the planned positions based on the digitally reconstructed radiographs (DRRs). An in‐house program was designed to measure left anterior descending artery (LAD) and chest wall separation on the planning DIBH CT scan with respect to breath‐hold level (BHL) during simulation to determine a minimum BHL for VM‐DIBH eligibility. Systematic and random setup uncertainties of 3.0 mm and 2.6 mm, respectively, were found for VM‐DIBH treatment from the chest wall measurements. Intrabeam breath‐hold stability was found to be good, with over 96% of delivered fields within 3 mm. Average treatment MHD was significantly larger for those patients where some of the heart was planned in the field compared to patients whose heart was completely shielded in the plan (p < 0.001). No evidence for a minimum BHL was found, suggesting that all patients who can tolerate DIBH may yield a benefit from it.

PACS number(s): 87.53.Jw, 87.53.Kn, 87.55.D‐
Rounded leaf end modeling in Pinnacle VMAT treatment planning for fixed jaw linacs
Authors: Young Lori A. , Yang Fei , Cao Ning , Meyer Juergen
Published: February 2017

During volume‐modulated arc therapies (VMAT), dosimetric errors are introduced by multiple open dynamic leaf gaps that are present in fixed diaphragm linear accelerators. The purpose of this work was to develop a methodology for adjusting the rounded leaf end modeling parameters to improve out‐of‐field dose agreement in SmartArc VMAT treatment plans delivered by fixed jaw linacs where leaf gap dose is not negligible. Leaf gap doses were measured for an Elekta beam modulator linac with 0.4 cm micro‐multileaf collimators (MLC) using an A16 micro‐ionization chamber, a MatriXX ion chamber detector array, and Kodak EDR2 film dosimetry in a solid water phantom. The MLC offset and rounded end tip radius were adjusted in the Pinnacle treatment planning system (TPS) to iteratively arrive at the optimal configuration for 6 MV and 10 MV photon energies. Improvements in gamma index with a acceptance criteria and an inclusion threshold of 5% of maximum dose were measured, analyzed, and validated using an ArcCHECK diode detector array for field sizes ranging from 1.6 to 14 cm square field arcs and Task Group (TG) 119 VMAT test cases. The best results were achieved for a rounded leaf tip radius of 13 cm with a 0.1 cm MLC offset. With the optimized MLC model, measured gamma indices ranged between 99.9% and 91.7% for square field arcs with sizes between 3.6 cm and 1.6 cm, with a maximum improvement of 42.7% for the 1.6 cm square field size. Gamma indices improved up to 2.8% in TG‐119 VMAT treatment plans. Imaging and Radiation Oncology Core (IROC) credentialing of a VMAT plan with the head and neck phantom passed with a gamma index of 100%. Fine‐tune adjustments to MLC rounded leaf ends may improve patient‐specific QA pass rates and provide more accurate predictions of dose deposition to avoidance structures.

PACS number(s): 87.55.D‐, 87.55.kd, 87.55.kh
Development of a universal medical X‐ray imaging phantom prototype
Authors: Groenewald Annemari , Groenewald Willem A.
Published: February 2017

Diagnostic X‐ray imaging depends on the maintenance of image quality that allows for proper diagnosis of medical conditions. Maintenance of image quality requires quality assurance programs on the various X‐ray modalities, which consist of projection radiography (including mobile X‐ray units), fluoroscopy, mammography, and computed tomography (CT) scanning. Currently a variety of modality‐specific phantoms are used to perform quality assurance (QA) tests. These phantoms are not only expensive, but suitably trained personnel are needed to successfully use them and interpret the results. The question arose as to whether a single universal phantom could be designed and applied to all of the X‐ray imaging modalities. A universal phantom would reduce initial procurement cost, possibly reduce the time spent on QA procedures and simplify training of staff on the single device. The aim of the study was to design and manufacture a prototype of a universal phantom, suitable for image quality assurance in general X‐rays, fluoroscopy, mammography, and CT scanning. The universal phantom should be easy to use and would enable automatic data analysis, pass/fail reporting, and corrective action recommendation. In addition, a universal phantom would especially be of value in low‐income countries where finances and human resources are limited. The design process included a thorough investigation of commercially available phantoms. Image quality parameters necessary for image quality assurance in the different X‐ray imaging modalities were determined. Based on information obtained from the above‐mentioned investigations, a prototype of a universal phantom was developed, keeping ease of use and reduced cost in mind. A variety of possible phantom housing and insert materials were investigated, considering physical properties, machinability, and cost. A three‐dimensional computer model of the first phantom prototype was used to manufacture the prototype housing and inserts. Some of the inserts were 3D‐printed, others were machined from different materials. The different components were assembled to form the first prototype of the universal X‐ray imaging phantom. The resulting prototype of the universal phantom conformed to the aims of a single phantom for multiple imaging modalities, which would be easy to use and manufacture at a reduced cost. A PCT International Patent Application No. PCT/IB2016/051165 has been filed for this technology.

PACS number(s): 87.57.C, 87.59.‐e
Production and quality control 177Lu (NCA)—DOTMP as a potential agent for bone pain palliation
Authors: Salek Nafise , Shamsaei Mojtaba , Maragheh Mohammad Ghannadi , Arani Simindokht Shirvani , Samani Ali Bahrami
Published: February 2017

Skeletal uptake of radiolabeled‐1, 4, 7, 10‐tetraazacyclododecane‐1, 4, 7, 10‐tetramethylene phosphoric acid (e.g., 177Lu‐DOTMP) complex, is used for bone pain palliation. The moderate energy of β‐emitting has been considered as a potential radionuclide for development of the bone‐seeking radiopharmaceutical. Since the specific activity of the radiolabeled carrier molecules should be high, the “no‐carrier‐added radionuclides” have significant roles in nuclear medicine. Many researchers illustrated no‐carrier‐added 177Lu production; among these separation techniques such as ion exchange chromatography, reversed phase ion‐pair, and electrochemical method, extraction chromatography has been considered more capable than other methods. In order to optimize the conditions, some effective factors on separation of Lu/Yb were investigated by EXC. The NCA 177Lu, produced by this method, was mixed with of DOTMP solution (20 mg in 1 mL of 0.5 M NaHCO3, ) and incubated under stirring at room temperature for 45 min. Radiochemical purity of the 177Lu‐DOTMP complex was determined using radio‐thin‐layer chromatography (RTLC) method. The complex was injected to wild‐type rats and biodistribution was then studied for seven days. The NCA 177Lu was produced with specific activity of 48 Ci/mg and with a radinuclidic purity of 99.99% through irradiation of enriched 176Yb target (1 mg) in a thermal neutron flux of for 14 days. 177Lu‐DOTMP was obtained with high radiochemical purities () under optimized reaction conditions. The radiolabeled complex exhibited excellent stability at room temperature. Biodistribution of the radiolabeled complex studies in rats showed favorable selective skeletal uptake with rapid clearance from blood along with insignificant accumulation within the other nontargeted organs.

PACS number(s): 87.57.un, 87.57.uq
A comparison of methods for monitoring photon beam energy constancy
Authors: Gao Song , Balter Peter A. , Rose Mark , Simon William E.
Published: February 2017

In extension of a previous study, we compared several photon beam energy metrics to determine which was the most sensitive to energy change; in addition to those, we accounted for both the sensitivity of each metric and the uncertainty in determining that metric for both traditional flattening filter (FF) beams (4, 6, 8, and 10 MV) and for flattening filter‐free (FFF) beams (6 and 10 MV) on a Varian TrueBeam. We examined changes in these energy metrics when photon energies were changed to and from their nominal energies: 1) an attenuation‐based metric (the percent depth dose at 10 cm depth, PDD(10)) and, 2) profile‐based metrics, including flatness (Flat) and off‐axis ratios (OARs) measured on the orthogonal axes or on the diagonals (diagonal normalized flatness, ). Profile‐based metrics were measured near and also near 10 cm depth in water (using a 3D scanner) and with ionization chamber array (ICA). PDD(10) was measured only in water. Changes in PDD, OAR, and were nearly linear to the changes in the bend magnet current (BMI) over the range from to +10% for both FF and FFF beams: a change in energy resulted in a change in PDD(10) for both FF and FFF beams, and changes in OAR and were for FF beams and for FFF beams. The uncertainty in determining PDD(10) was estimated to be 0.15% and that for OAR and about 0.07%. This resulted in minimally detectable changes in energy of 2.5% for PDD(10) and 0.5% for OAR and . We found that the OAR‐ or FDN‐ based metrics were the best for detecting energy changes for both FF and FFF beams. The ability of the OAR‐based metrics determined with a water scanner to detect energy changes was equivalent to that using an ionization chamber array. We recommend that OAR be measured either on the orthogonal axes or the diagonals, using an ionization chamber array near the depth of maximum dose, as a sensitive and efficient way to confirm stability of photon beam energy.

PACS number(s): 87.55.Qr, 87.56.Fc
Far-field coherent backscatter enhancement from random aggregations of scatterers and comparisons to backscattering from single isolated spheres
Authors: Mookerjee Adaleena , Dowling David R.
Published: February 2017

Coherent backscatter enhancement (CBE), a multiple scattering phenomenon, may cause an enhancement of up to a factor of two in the average intensity backscattered from a random aggregation of scatterers. In the ocean, CBE may occur when a fish school or a bubble cloud is remotely illuminated. The research reported here explored the possibility that CBE might be used to remotely discriminate between an aggregation of many scatterers and a single isolated scattering object. For this investigation, the far-field harmonic acoustic pressure backscattered from aggregations of randomly placed omnidirectional point scatterers was determined from numerical solution of the equations from Foldy [(1945) Phys. Rev. 67(3,4), 107–119], and compared to equivalent results from single spherical scatterers having hard surfaces, pressure-release surfaces, or aggregation-matched effective-medium properties. Interestingly, CBE causes a spherical aggregation to backscatter as much or more sound than a single perfectly reflecting sphere of the same size when (ka)1/2(ks)−4/5(kσs1/2)3/4 ≥ 2.3, where k is the acoustic wave number, a is the aggregation radius, s is the average spacing between scatterers, and σs is a scatterer's cross section. And, backscattered intensity samples (in dB) from all simulated aggregations followed an extreme value distribution, a finding that supports the conventional use of backscatter statistics for remote aggregation-versus-single-object discrimination.
Accurate group velocity estimation for unmanned aerial vehicle-based acoustic atmospheric tomography
Authors: Rogers Kevin J. , Finn Anthony
Published: February 2017

Acoustic atmospheric tomography calculates temperature and wind velocity fields in a slice or volume of atmosphere based on travel time estimates between strategically located sources and receivers. The technique discussed in this paper uses the natural acoustic signature of an unmanned aerial vehicle as it overflies an array of microphones on the ground. The sound emitted by the aircraft is recorded on-board and by the ground microphones. The group velocities of the intersecting sound rays are then derived by comparing these measurements. Tomographic inversion is used to estimate the temperature and wind fields from the group velocity measurements. This paper describes a technique for deriving travel time (and hence group velocity) with an accuracy of 0.1% using these assets. This is shown to be sufficient to obtain highly plausible tomographic inversion results that correlate well with independent SODAR measurements.
Establishment of an AUC
0–24
Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Chavada R. , Ghosh N. , Sandaradura I. , Maley M. , Van Hal S. J.
Published: February 2017

Unlike vancomycin trough concentrations, data on the utility of vancomycin pharmacokinetic (PK) parameters, namely, the area under the concentration-time curve from 0 to 24 h (AUC
0–24
), in predicting acute kidney injury (AKI) are limited. Our aim was to investigate this relationship in patients receiving vancomycin therapy for methicillin-resistant
Staphylococcus aureus
bacteremia (MRSA-B). A single-center retrospective observational cohort study involving 127 consecutive MRSA-B patients was conducted to examine the incidence of AKI (defined as serum creatinine of ≥0.5 mg/liter and a 50% increase from baseline) and vancomycin exposure parameters associated with nephrotoxicity. Bayesian estimation was used to predict individual vancomycin AUC
0–24
. All patients received vancomycin monotherapy for a minimum of 14 days following the diagnosis of MRSA-B. AKI was observed in 15.7% of patients (20/127). Clinical characteristics were similar between patients with and without AKI. At steady state, higher vancomycin trough concentrations were associated with AKI (17.2 mg/liter versus 13.1 mg/liter;
P
= 0.003). A vancomycin AUC
0–24
threshold for AKI of >563 mg · h/liter was detected by classification and regression tree (CART) analysis; patients with exposures above this threshold were significantly more likely to experience AKI than patients with lower vancomycin exposures (40% [8/20] versus 11.2% [12/107];
P
= 0.002). This parameter remained an independent predictor of AKI on multivariate logistic regression (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.57 to 16.29;
P
= 0.006) and was a better predictor of nephrotoxicity than vancomycin trough concentrations. Overall, AKI is associated with higher vancomycin exposure as measured by AUC
0–24
. These results suggest that individualized patient dosing may be possible with dose modifications directed toward established pharmacodynamic targets while balancing AKI risks.
Adjuvant Antibiotic Activity of Acidic Sophorolipids with Potential for Facilitating Wound Healing
Authors: Lydon Helen L. , Baccile Niki , Callaghan Breedge , Marchant Roger , Mitchell Christopher A. , Banat Ibrahim M.
Published: February 2017

The sophorolipid class of biosurfactants is finding increasing use in personal care as well as pharmaceutical products and has the potential to disrupt biofilm formation and inhibit the growth of a variety of clinically relevant organisms. In order to investigate potential biomedical applications of sophorolipids derived from nonpathogenic organisms, we fractionated and purified glycolipid biosurfactant sophorolipids produced by the yeast
Starmerella bombicola
, which yielded nonacetylated acidic C
18:1
congeners that were essentially free from other contaminants (>95% purity). These acidic sophorolipids have antimicrobial activities against the nosocomial infective agents
Enterococcus faecalis
and
Pseudomonas aeruginosa
, with significant reductions in CFU at concentrations of as low as 5 mg ml
−1
. In addition, the sophorolipid showed similar effects against the same two bacterial strains when combined with kanamycin or cefotaxime. As a potential use of these sophorolipids is as a component of topically applied creams for the treatment of wound infections, it is clear that they must have no demonstrable adverse effect on wound healing. To assess this, we evaluated mammalian cell toxicity
in vitro
using viability tests, which revealed no adverse effect on either endothelial or keratinocyte-derived cell lines with sophorolipid concentrations of < 0.5 mg ml
−1
. In addition,
in vivo
experiments using a mouse skin wounding assay revealed that the time course of healing wounds was unaffected by the application of sophorolipid-containing creams, and histological examination of regenerated skin tissue confirmed that the healing process was similar to that observed for control animals, with no evidence of inflammation. These results are consistent with the suggestion that acidic sophorolipids can be used as a component of antimicrobial creams to reduce the risk of wound infection during healing.
Nitrotriazole-Based Compounds as Antichagasic Agents in a Long-Treatment
In Vivo
Assay
Authors: Papadopoulou Maria V. , Bloomer William D. , Rosenzweig Howard S. , Mazzeti Ana Lia , Gonçalves Karolina Ribeiro , Mendes Priscila Fagundes , Bahia Maria Terezinha
Published: February 2017

3-Nitrotriazole-based compounds belonging to various chemical subclasses were found to be very effective against Chagas disease both
in vitro
and
in vivo
after a short administration schedule. In this study, five compounds with specific characteristics were selected to be administered for longer periods of time to mice infected with the virulent
Trypanosoma cruzi
Y strain to further evaluate their effectiveness as antichagasic agents and whether or not potential adverse effects occur. Benznidazole was included for comparison purposes. Complete parasitemia depletion, weight gain, 100% survival, and a lack of myocardial inflammation were observed with four of the compounds and benznidazole administered intraperitoneally at 15 or 20 mg/kg of body weight/day for 40 days. There was a significant reduction in the number of treatment days (number of doses) necessary to induce parasitemia suppression with all four compounds compared to that required with benznidazole. Partial cures were obtained with only one compound tested at 15 mg/kg/day and on the schedule mentioned above but not with benznidazole. Taken together, our data suggest that these compounds demonstrate potent trypanocidal activity comparable to or better than that of the reference drug, benznidazole, when they are administered at the same dose and on the same schedule.
Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens
Authors: Hendrick William A. , Orr Mona W. , Murray Samantha R. , Lee Vincent T. , Melville Stephen B.
Published: February 2017

The Gram-positive pathogen
Clostridium perfringens
possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in
C. perfringens
, called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the
pilB2
and
pilC2
genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected
in vivo
or
in vitro
even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from
C. perfringens
(CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels
in vivo
but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from
in vivo
studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium.

IMPORTANCE
Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species
Clostridium perfringens
was used to study proteins involved in polymerizing the pilin, PilA2, into a pilus. The assembly ATPase PilB2 and its cognate membrane protein partner, PilC2, were purified. PilB2 bound the intracellular signal molecule c-di-GMP. Increased levels of intracellular c-di-GMP led to increased polymerization of PilA2, indicating that Gram-positive bacteria use this molecule to regulate pilus synthesis. These findings provide valuable information for understanding how pathogenic clostridia regulate TFP to cause human diseases.
Understanding the Models of Community Hospital rehabilitation Activity (MoCHA): a mixed-methods study
Authors: Gladman John , Buckell John , Young John , Smith Andrew , Hulme Clare , Saggu Satti , Godfrey Mary , Enderby Pam , Teale Elizabeth , Longo Roberto , Gannon Brenda , Holditch Claire , Eardley Heather , Tucker Helen
Published: February 2017

Introduction

To understand the variation in performance between community hospitals, our objectives are: to measure the relative performance (cost efficiency) of rehabilitation services in community hospitals; to identify the characteristics of community hospital rehabilitation that optimise performance; to investigate the current impact of community hospital inpatient rehabilitation for older people on secondary care and the potential impact if community hospital rehabilitation was optimised to best practice nationally; to examine the relationship between the configuration of intermediate care and secondary care bed use; and to develop toolkits for commissioners and community hospital providers to optimise performance.

Methods and analysis

4 linked studies will be performed. Study 1: cost efficiency modelling will apply econometric techniques to data sets from the National Health Service (NHS) Benchmarking Network surveys of community hospital and intermediate care. This will identify community hospitals' performance and estimate the gap between high and low performers. Analyses will determine the potential impact if the performance of all community hospitals nationally was optimised to best performance, and examine the association between community hospital configuration and secondary care bed use. Study 2: a national community hospital survey gathering detailed cost data and efficiency variables will be performed. Study 3: in-depth case studies of 3 community hospitals, 2 high and 1 low performing, will be undertaken. Case studies will gather routine hospital and local health economy data. Ward culture will be surveyed. Content and delivery of treatment will be observed. Patients and staff will be interviewed. Study 4: co-designed web-based quality improvement toolkits for commissioners and providers will be developed, including indicators of performance and the gap between local and best community hospitals performance.

Ethics and dissemination

Publications will be in peer-reviewed journals, reports will be distributed through stakeholder organisations. Ethical approval was obtained from the Bradford Research Ethics Committee (reference: 15/YH/0062).
Early warning of footpad dermatitis and hockburn in broiler chicken flocks using optical flow, bodyweight and water consumption
Authors: Dawkins M. S. , Roberts S. J. , Cain R. J. , Nickson T. , Donnelly C. A.
Published: February 2017

Footpad dermatitis and hockburn are serious welfare and economic issues for the production of broiler (meat) chickens. The authors here describe the use of an inexpensive camera system that monitors the movements of broiler flocks throughout their lives and suggest that it is possible to predict, even in young birds, the cross‐sectional prevalence at slaughter of footpad dermatitis and hockburn before external signs are visible. The skew and kurtosis calculated from the authors’ camera‐based optical flow system had considerably more power to predict these outcomes in the 50 flocks reported here than water consumption, bodyweight or mortality and therefore have the potential to inform improved flock management through giving farmers early warning of welfare issues. Further trials are underway to establish the generality of the results.
Power coupling characteristics between FBG and back-scattering signals
Authors: Li Jianzhi , Zhao Desheng , Hou Yuemin , Sun Baochen
Published: February 2017

The property and compatibility between fiber Bragg grating (FBG) and back-scattering signals are investigated by employing optical time domain reflectometry. We compare the power spectrums of spontaneous Brillouin scattering (SpBS), simultaneous Brillouin scattering (SBS) and Rayleigh scattering (RS), and coupling mechanism between FBG and back-scattering signal is explored. Experimental results show that the region of FBG contributes to the backscatter power and causes the desired reflection, and the power peak of FBG in SBS power spectrum is the sharpest among back-scattering light power spectrums and broadens with the decrease of spatial resolution. Moreover, the FBG-based method is used to find the location of temperature or stain event for scatter-based distributed sensors.
Research and analysis on the broadband dispersion tailoring of the sub-micro silicon-on-insulator waveguides
Authors: Wen Jin , Liu Wang , Liu Keyang , Fu Haiwei , Jia Zhenan
Published: February 2017

High-order dispersions of the silicon-on-insulator (SOI) waveguides with different shapes (including slab, ridge and slot) have been obtained and compared using the finite element method (FEM). Through adjusting the geometrical parameters of the waveguides, single or dual zero-dispersion wavelengths (ZDWs) can be tuned in the broadband wavelength range. Differences of dispersion curves among these waveguides are analyzed from the viewpoint of structure and mechanism in detail. It is remarkably shown the number of ZDWs can be varied from 0 to 2 and the position of the ZDWs can be tuned from 1400 nm to 1900 nm flexibly. Moreover, the differences of dispersion features in short and long wavelength regions are also discussed deeply. Due to the dispersion of SOI waveguides playing a dominated role in many nonlinear optical effects, this research can make some contribution for dispersion tailoring and nonlinear optics.
A temperature characteristic research and compensation design for micro-machined gyroscope
Authors: Fu Qiang , Di Xin-Peng , Chen Wei-Ping , Yin Liang , Liu Xiao-Wei
Published: February 2017

The all temperature range stability is the most important technology of MEMS angular velocity sensor according to the principle of capacity detecting. The correlation between driven force and zero-point of sensor is summarized according to the temperature characteristic of the air-damping and resonant frequency of sensor header. A constant trans-conductance high-linearity amplifier is designed to realize the low phase-drift and low amplitude-drift interface circuit at all-temperature range. The chip is fabricated in a standard 0.5 [Formula: see text] CMOS process. Compensation achieved by driven force to zero-point drift caused by the stiffness of physical construction and air-damping is adopted. Moreover, the driven force can be obtained from the drive-circuit to avoid the complex sampling. The test result shows that the zero-point drift is lower than 30[Formula: see text]/h (1-sigma) at the temperature range from −40[Formula: see text]C to 60[Formula: see text]C after three-order compensation made by driven force.
Exact and Hybrid Solutions for the Multi-Objective VM Reassignment Problem
Authors: Saber Takfarinas , Marques-Silva Joao , Thorburn James , Ventresque Anthony
Published: February 2017

Machine Reassignment is a challenging problem for constraint programming (CP) and mixed integer linear programming (MILP) approaches, especially given the size of data centres. Hybrid solutions mixing CP and heuristic algorithms, such as, large neighbourhood search (CBLNS), also struggle to address the problem given its size and number of constraints. The multi-objective version of the Machine Reassignment Problem is even more challenging and it seems unlikely for CP, MILP or hybrid solutions to obtain good results in this context. As a result, the first approaches to address this problem have been based on other optimisation methods, including metaheuristics. In this paper we study three things: (i) under which conditions a mixed integer optimisation solver, such as IBM ILOG CPLEX, can be used for the Multi-objective Machine Reassignment Problem; (ii) how much of the search space can a well-known hybrid method such as CBLNS explore; and (iii) can we find a better hybrid approach combining MILP or CBLNS and an- other recent metaheuristic proposed for the problem (GeNePi). We show that MILP can handle only small or medium scale data centres, and with some relaxations, such as, an optimality tolerance gap and a limited number of directions explored in the search space. CBLNS on the other hand struggles with the problem in general but achieves reasonable performance for large instances of the problem. However, we show that our hybridisation improves both the quality of the set of solutions (CPLEX+GeNePi and CBLNS+GeNePi improve the solutions by +17.8% against CPLEX alone and +615% against CBLNS alone) and number of solutions (8.9 times more solutions than CPLEX alone and 56.76 times more solutions than CBLNS alone), while the processing time of CPLEX+GeNePi and CBLNS+GeNePi increases only by 6% and 16.4% respectively. Overall, the study shows that CPLEX+GeNePi is the best algorithm for small instances (CBLNS+GeNePi only gets 45.2% of CPLEX+GeNePi’s hypervolume) while CBLNS+GeNePi is better than the others on large instances (that CPLEX+GeNePi cannot address).
Reciprocal Social Strategy in Social Repeated Games and Emergence of Social Norms
Authors: Chan Chi-Kong , Hao Jianye , Leung Ho-Fung
Published: February 2017

In an artificial society where agents repeatedly interact with one another, effective coordination among agents is generally a challenge. This is especially true when the participating agents are self-interested, and that there is no central authority to coordinate, and direct communication or negotiation are not possible. Recently, the problem was studied in a paper by Hao and Leung, where a new repeated game mechanism for modeling multi-agent interactions as well as a new reinforcement learning based agent learning method were proposed. In particular, the game mechanism differs from traditional repeated games in that the agents are anonymous, and the agents interact with randomly chosen opponents during each iteration. Their learning mechanism allows agents to coordinate without negotiations. The initial results had been promising. However, extended simulation also reveals that the outcomes are not stable in the long run in some cases, as the high level of cooperation is eventually not sustainable. In this work, we revisit he problem and propose a new learning mechanism as follows. First, we propose an enhanced Q-learning-based framework that allows the agents to better capture both the individual and social utilities that they have learned through observations. Second, we propose a new concept of \social attitude" for determining the action of the agents throughout the game. Simulation results reveal that this approach can achieve higher social utility, including close-to-optimal results in some scenarios, and more importantly, the results are sustainable with social norms emerging.
Heuristic and Genetic Algorithm Approaches for UAV Path Planning under Critical Situation
Authors: Silva Arantes Jesimar da , Silva Arantes Márcio da , Motta Toledo Claudio Fabiano , Júnior Onofre Trindade , Williams Brian Charles
Published: February 2017

The present paper applies a heuristic and genetic algorithms approaches to the path planning problem for Unmanned Aerial Vehicles (UAVs), during an emergency landing, without putting at risk people and properties. The path re-planning can be caused by critical situations such as equipment failures or extreme environmental events, which lead the current UAV mission to be aborted by executing an emergency landing. This path planning problem is introduced through a mathematical formulation, where all problem constraints are properly described. Planner algorithms must define a new path to land the UAV following problem constraints. Three path planning approaches are introduced: greedy heuristic, genetic algorithm and multi-population genetic algorithm. The greedy heuristic aims at quickly find feasible paths, while the genetic algorithms are able to return better quality solutions within a reasonable computational time. These methods are evaluated over a large set of scenarios with different levels of diffculty. Simulations are also conducted by using FlightGear simulator, where the UAV’s behaviour is evaluated for different wind velocities and wind directions. Statistical analysis reveal that combining the greedy heuristic with the genetic algorithms is a good strategy for this problem.
Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse
Authors: Vanichtantikul Asama , Tharavichitkul Ekkasit , Chitapanarux Imjai , Chinthakanan Orawee
Published: February 2017

Background. Uterine malignancy coexistent with pelvic organ prolapse (POP) is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.
A Rare Case of Stroke Secondary to Iron Deficiency Anemia in a Young Female Patient
Authors: Gopalratnam Kavitha , Woodson Kevin Andrew , Rangunwala Jigarkumar , Sena Kanaga , Gupta Manisha
Published: February 2017

Ischemic strokes occur when there is a sudden obstruction of an artery supplying blood flow to an area of the brain, leading to a focal neurological deficit. Strokes can be thrombotic or embolic in etiology and are associated with underlying conditions such as hypertension and atherosclerosis. Possible etiologies of strokes include cardioembolic disease, hematologic disorders, connective tissue disorders, and substance abuse or can be cryptogenic. Most stroke cases are seen in patients over 65 years of age. However, about one-fourth of strokes occur in young adults. Iron deficiency anemia (IDA) has been described as a known cause for strokes in children, but very few case reports describe this association in adults. We describe a 20-year-old female who presented with sudden onset left side weakness. Magnetic Resonance Imaging (MRI) of the brain demonstrated ischemic infarctions. Patient was also found to be severely anemic. Patient had a thorough work-up including Magnetic Resonance Angiography (MRA) of the brain, echocardiogram, and an extensive screen for thrombophilia disorders. This, however, did not demonstrate a clear etiology. As it has been suggested that IDA is a potential cause for stroke, it is possible the stroke in this young patient was attributable to severe IDA.
An Efficient Platform for the Automatic Extraction of Patterns in Native Code
Authors: Escalada Javier , Ortin Francisco , Scully Ted
Published: February 2017

Different software tools, such as decompilers, code quality analyzers, recognizers of packed executable files, authorship analyzers, and malware detectors, search for patterns in binary code. The use of machine learning algorithms, trained with programs taken from the huge number of applications in the existing open source code repositories, allows finding patterns not detected with the manual approach. To this end, we have created a versatile platform for the automatic extraction of patterns from native code, capable of processing big binary files. Its implementation has been parallelized, providing important runtime performance benefits for multicore architectures. Compared to the single-processor execution, the average performance improvement obtained with the best configuration is 3.5 factors over the maximum theoretical gain of 4 factors.