bluuebunny/crossref_metadata_2025 huggingface dataset:
TH‐EF‐BRB‐04: 4π Dynamic Conformal Arc Therapy Dynamic Conformal Arc Therapy (DCAT) for SBRT
Authors: Chiu T , Long T , Modiri A , Tian Z. , Sawant A , Yan Y , Jiang S , Gu X
Published: July 2016

Purpose:

To develop an efficient and effective trajectory optimization methodology for 4π dynamic conformal arc treatment (4π DCAT) with synchronized gantry and couch motion; and to investigate potential clinical benefits for stereotactic body radiation therapy (SBRT) to breast, lung, liver and spine tumors.

Methods:

The entire optimization framework for 4π DCAT inverse planning consists of two parts: 1) integer programming algorithm and 2) particle swarm optimization (PSO) algorithm. The integer programming is designed to find an optimal solution for arc delivery trajectory with both couch and gantry rotation, while PSO minimize a non‐convex objective function based on the selected trajectory and dose‐volume constraints. In this study, control point interaction is explicitly taken into account. Beam trajectory was modeled as a series of control points connected together to form a deliverable path. With linear treatment planning objectives, a mixed‐integer program (MIP) was formulated. Under mild assumptions, the MIP is tractable. Assigning monitor units to control points along the path can be integrated into the model and done by PSO. The developed 4π DCAT inverse planning strategy is evaluated on SBRT cases and compared to clinically treated plans.

Results:

The resultant dose distribution of this technique was evaluated between 3D conformal treatment plan generated by Pinnacle treatment planning system and 4π DCAT on a lung SBRT patient case. Both plans share the same scale of MU, 3038 and 2822 correspondingly to 3D conformal plan and 4π DCAT. The mean doses for most of OARs were greatly reduced at 32% (cord), 70% (esophagus), 2.8% (lung) and 42.4% (stomach).

Conclusion:

Initial results in this study show the proposed 4π DCAT treatment technique can achieve better OAR sparing and lower MUs, which indicates that the developed technique is promising for high dose SBRT to reduce the risk of secondary cancer.
TH‐EF‐BRB‐09: Total Body Irradiation with Uniform MU and Modulated Arc Segments, UMMS‐TBI
Authors: Yi B , Chung H , Mutaf Y , Prado K
Published: July 2016

Purpose:

To test a novel total body irradiation (TBI) system using conformal partial arc with patient lying on the stationary couch which is biologically equivalent to a moving couch TBI. This improves the scanning field TBI, which is previously presented.

Methods:

The Uniform MU Modulated arc Segments TBI or UMMS‐TBI scans the treatment plane with a constant machine dose rate and a constant gantry rotation speed. A dynamic MLC pattern which moves while gantry rotates has been designed so that the treatment field moves same distance at the treatment plane per each gantry angle, while maintaining same treatment field size (34cm) at the plane. Dose across the plane varies due to the geometric differences including the distance from the source to a point of interest and the different attenuation from the slanted depth which changes the effective depth. Beam intensity is modulated to correct the dose variation across the plane by assigning the number of gantry angles inversely proportional to the uncorrected dose.

Results:

Measured dose and calculated dose matched within 1 % for central axis and 3% for off axis for various patient scenarios. Dose from different distance does not follow the inverse square relation as it is predicted from calculation. Dose uniformity better than 5% across 180 cm at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 200 MU/min.

Conclusion:

This novel technique, yet accurate but easy to implement enables TBI treatment in a small treatment room with less program development preparation than other techniques. The VMAT function of treatment delivery is not required to modulate beams. One delivery pattern can be used for different patients by changing the monitor units.
TH‐EF‐BRA‐05: A MethodÂ of Near Real‐Time 4D MRI Using Volumetric Dynamic Keyhole (VDK) in the Presence of Respiratory Motion for MR‐Guided Radiotherapy
Authors: Lewis B , Kim S , Kim T
Published: July 2016

Purpose:

To develop a novel method that enables 4D MR imaging in near real‐time for continuous monitoring of tumor motion in MR‐guided radiotherapy.

Methods:

This method is mainly based on an idea of expanding dynamic keyhole to full volumetric imaging acquisition. In the VDK approach introduced in this study, a library of peripheral volumetric k‐space data is generated in given number of phases (5 and 10 in this study) in advance. For 4D MRI at any given time, only volumetric central k‐space data are acquired in real‐time and combined with pre‐acquired peripheral volumetric k‐space data in the library corresponding to the respiratory phase (or amplitude). The combined k‐space data are Fourier‐transformed to MR images. For simulation study, an MRXCAT program was used to generate synthetic MR images of the thorax with desired respiratory motion, contrast levels, and spatial and temporal resolution. 20 phases of volumetric MR images, with 200 ms temporal resolution in 4 s respiratory period, were generated using balanced steady‐state free precession MR pulse sequence. The total acquisition time was 21.5s/phase with a voxel size of 3×3×5 mm3 and an image matrix of 128×128×56. Image similarity was evaluated with difference maps between the reference and reconstructed images. The VDK, conventional keyhole, and zero filling methods were compared for this simulation study.

Results:

Using 80% of the ky data and 70% of the kz data from the library resulted in 12.20% average intensity difference from the reference, and 21.60% and 28.45% difference in threshold pixel difference for conventional keyhole and zero filling, respectively. The imaging time will be reduced from 21.5s to 1.3s per volume using the VDK method.

Conclusion:

Near real‐time 4D MR imaging can be achieved using the volumetric dynamic keyhole method. That makes the possibility of utilizing 4D MRI during MR‐guided radiotherapy.
TH‐EF‐BRA‐06: A Novel Retrospective 3D K‐Space Sorting 4D‐MRI Technique Using a Radial K‐Space Acquisition MRI Sequence
Authors: Liu Y , Subashi E , Yin F , Cai J
Published: July 2016

Purpose:

Current retrospective 4D‐MRI provides superior tumor‐to‐tissue contrast and accurate respiratory motion information for radiotherapy motion management. The developed 4D‐MRI techniques based on 2D‐MRI image sorting require a high frame‐rate of the MR sequences. However, several MRI sequences provide excellent image quality but have low frame‐rate. This study aims at developing a novel retrospective 3D k‐space sorting 4D‐MRI technique using radial k‐space acquisition MRI sequences to improve 4D‐MRI image quality and temporal‐resolution for imaging irregular organ/tumor respiratory motion.

Methods:

The method is based on a RF‐spoiled, steady‐state, gradient‐recalled sequence with minimal echo time. A 3D radial k‐space data acquisition trajectory was used for sampling the datasets. Each radial spoke readout data line starts from the 3D center of Field‐of‐View. Respiratory signal can be extracted from the k‐space center data point of each spoke. The spoke data was sorted based on its self‐synchronized respiratory signal using phase sorting. Subsequently, 3D reconstruction was conducted to generate the time‐resolved 4D‐MRI images. As a feasibility study, this technique was implemented on a digital human phantom XCAT. The respiratory motion was controlled by an irregular motion profile. To validate using k‐space center data as a respiratory surrogate, we compared it with the XCAT input controlling breathing profile. Tumor motion trajectories measured on reconstructed 4D‐MRI were compared to the average input trajectory. The mean absolute amplitude difference (D) was calculated.

Results:

The signal extracted from k‐space center data matches well with the input controlling respiratory profile of XCAT. The relative amplitude error was 8.6% and the relative phase error was 3.5%. XCAT 4D‐MRI demonstrated a clear motion pattern with little serrated artifacts. D of tumor trajectories was 0.21mm, 0.23mm and 0.23mm in SI, AP and ML directions, respectively.

Conclusion:

A novel retrospective 3D k‐space sorting 4D‐MRI technique has been developed and evaluated on human digital phantom.

NIH (1R21CA165384‐01A1)
TH‐EF‐BRA‐10: High Spatiotemporal Resolution Self‐Sorted 4D MRI
Authors: Subashi E , Liu Y , Robertson S , Segars P , Driehuys B , Yin F , Cai J
Published: July 2016

Purpose:

To describe a novel method for self‐sorted 4D‐MRI and to characterize the output image quality as measured by signal‐to‐noise ratio (SNR), spatiotemporal resolution, and level of artifact.

Methods:

A three‐dimensional radial sampling function with a quasi‐random distribution of polar/azimuthal k‐space angles was implemented in a standard pulse sequence. Acquisition time was approximately 2 minutes. The DC component of the k‐space signal was used to estimate and sort the breathing cycle into ten respiratory phases. For a given respiratory phase, the k‐space data were combined with the periphery of the k‐space data from all phases and reconstructed with the re‐gridding algorithm onto a 1283 matrix. The extent of data sharing was controlled by the average breathing curve. The sampling and reconstruction technique were tested and validated in simulation, dynamic phantom, animal, and human studies with varying breathing periods/amplitudes.

Results:

The signal at the k‐space center accurately measures respiratory motion over a large range of breathing periods (0.5–7.0 seconds) and amplitudes (5–30% of FOV). Sharing of high frequency k‐space data driven by the average breathing curve improves spatial resolution and artifact level at a cost of an increase in noise floor. Although equal sharing of k‐space data improves resolution and SNR, phases with large temporal changes accumulate considerable distortion artifacts. In the absence of view‐sharing, no distortion artifacts are observed while spatial resolution is degraded.

Conclusion:

The use of a quasi‐random sampling function and view‐sharing driven by the average breathing curve provide a feasible method for self‐sorted 4D MRI at reduced acquisition times. This approach allows for the extent of data sharing to be inversely‐proportional to the average breathing motion hence improving resolution and decreasing artifact levels.

NIH‐1R21CA165384
TH‐EF‐BRA‐11: Feasibility of Super‐Resolution Time‐Resolved 4DMRI for Multi‐Breath Volumetric Motion Simulation in Radiotherapy Planning
Authors: Li G , Wei J , Zakian K , Hunt M , Deasy J
Published: July 2016

Purpose:

To develop a novel super‐resolution time‐resolved 4DMRI technique to evaluate multi‐breath, irregular and complex organ motion without respiratory surrogate for radiotherapy planning.

Methods:

The super‐resolution time‐resolved (TR) 4DMRI approach combines a series of low‐resolution 3D cine MRI images acquired during free breathing (FB) with a high‐resolution breath‐hold (BH) 3DMRI via deformable image registration (DIR). Five volunteers participated in the study under an IRB‐approved protocol. The 3D cine images with voxel size of 5×5×5 mm3 at two volumes per second (2Hz) were acquired coronally using a T1 fast field echo sequence, half‐scan (0.8) acceleration, and SENSE (3) parallel imaging. Phase‐encoding was set in the lateral direction to minimize motion artifacts. The BH image with voxel size of 2×2×2 mm3 was acquired using the same sequence within 10 seconds. A demons‐based DIR program was employed to produce super‐resolution 2Hz 4DMRI. Registration quality was visually assessed using difference images between TR 4DMRI and 3D cine and quantitatively assessed using average voxel correlation. The fidelity of the 3D cine images was assessed using a gel phantom and a 1D motion platform by comparing mobile and static images.

Results:

Owing to voxel intensity similarity using the same MRI scanning sequence, accurate DIR between FB and BH images is achieved. The voxel correlations between 3D cine and TR 4DMRI are greater than 0.92 in all cases and the difference images illustrate minimal residual error with little systematic patterns. The 3D cine images of the mobile gel phantom preserve object geometry with minimal scanning artifacts.

Conclusion:

The super‐resolution time‐resolved 4DMRI technique has been achieved via DIR, providing a potential solution for multi‐breath motion assessment. Accurate DIR mapping has been achieved to map high‐resolution BH images to low‐resolution FB images, producing 2Hz volumetric high‐resolution 4DMRI. Further validation and improvement are still required prior to clinical applications.

This study is in part supported by the NIH (U54CA137788/U54CA132378).
TH‐E‐202‐00: PET for Radiation Therapy
Authors: Lu Wei
Published: July 2016

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss:

Pitfalls and remedies in PET/CT imaging for RT planning

The use of hypoxia PET imaging for radiotherapy

PET for tumor response evaluation

The first presentation will address the issue of mis‐registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image‐guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de‐escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi‐quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non‐FDG PET tracers for response assessment.

Learning Objectives:

Identify the causes of mis‐registration of CT and PET images in PET/CT, and review the strategies to remedy the issue.

Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo‐radiation therapy).

Understand the basics of dynamic PET imaging, compartmental modeling and parametric images.

Understand the basics of using FDG PET/CT for tumor response evaluation.

Learn about recent advancement in PET/CT radiomics and non‐FDG PET tracers for response assessment.

This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.
TH‐E‐202‐03: PET for Tumor Response Evaluation
Authors: Lu W.
Published: July 2016

PET/CT is a very important imaging tool in the management of oncology patients. PET/CT has been applied for treatment planning and response evaluation in radiation therapy. This educational session will discuss:

Pitfalls and remedies in PET/CT imaging for RT planning

The use of hypoxia PET imaging for radiotherapy

PET for tumor response evaluation

The first presentation will address the issue of mis‐registration between the CT and PET images in the thorax and the abdomen. We will discuss the challenges of respiratory gating and introduce an average CT technique to improve the registration for dose calculation and image‐guidance in radiation therapy. The second presentation will discuss the use of hypoxia PET Imaging for radiation therapy. We will discuss various hypoxia radiotracers, the choice of clinical acquisition protocol (in particular a single late static acquisition versus a dynamic acquisition), and the compartmental modeling with different transfer rate constants explained. We will demonstrate applications of hypoxia imaging for dose escalation/de‐escalation in clinical trials. The last presentation will discuss the use of PET/CT for tumor response evaluation. We will discuss anatomic response assessment vs. metabolic response assessment, visual evaluation and semi‐quantitative evaluation, and limitations of current PET/CT assessment. We will summarize clinical trials using PET response in guiding adaptive radiotherapy. Finally, we will summarize recent advancements in PET/CT radiomics and non‐FDG PET tracers for response assessment.

Learning Objectives:

Identify the causes of mis‐registration of CT and PET images in PET/CT, and review the strategies to remedy the issue.

Understand the basics of PET imaging of tumor hypoxia (radiotracers, how PET measures the hypoxia selective uptake, imaging protocols, applications in chemo‐radiation therapy).

Understand the basics of dynamic PET imaging, compartmental modeling and parametric images.

Understand the basics of using FDG PET/CT for tumor response evaluation.

Learn about recent advancement in PET/CT radiomics and non‐FDG PET tracers for response assessment.

This work was supported in part by the National Cancer Institute Grants R01CA172638.; W. Lu, This work was supported in part by the National Cancer Institute Grants R01CA172638.
TH‐EF‐207A‐01: Respiratory Motion Correction in 4D‐Multi Pinhole Small Animal SPECT
Authors: Naseri M , Rajabi H , Wang J , Kalantari F
Published: July 2016

Purpose:

Respiration causes lesion smearing, image blurring and quality degradation, affecting lesion contrast and the ability to define correct lesion size. The spatial resolution of current multi pinhole SPECT (MPHS) scanners is sub‐millimeter. Therefore, the effect of motion is more noticeable in comparison to conventional SPECT scanner. Gated imaging aims to reduce motion artifacts. A major issue in gating is the lack of statistics and individual reconstructed frames are noisy. The increased noise in each frame, deteriorates the quantitative accuracy of the MPHS Images. The objective of this work, is to enhance the image quality in 4D‐MPHS imaging, by 4D image reconstruction.

Methods:

The new algorithm requires deformation vector fields (DVFs) that are calculated by non‐rigid Demons registration. The algorithm is based on the motion‐incorporated version of ordered subset expectation maximization (OSEM) algorithm. This iterative algorithm is capable to make full use of all projections to reconstruct each individual frame. To evaluate the performance of the proposed algorithm a simulation study was conducted. A fast ray tracing method was used to generate MPHS projections of a 4D digital mouse phantom with a small tumor in liver in eight different respiratory phases. To evaluate the 4D‐OSEM algorithm potential, tumor to liver activity ratio was compared with other image reconstruction methods including 3D‐MPHS and post reconstruction registered with Demons‐derived DVFs.

Results:

Image quality of 4D‐MPHS is greatly improved by the 4D‐OSEM algorithm. When all projections are used to reconstruct a 3D‐MPHS, motion blurring artifacts are present, leading to overestimation of the tumor size and 24% tumor contrast underestimation. This error reduced to 16% and 10% for post reconstruction registration methods and 4D‐OSEM respectively.

Conclusion:

4D‐OSEM method can be used for motion correction in 4D‐MPHS. The statistics and quantification are improved since all projection data are combined together to update the image.
TH‐EF‐207A‐07: An Integrated X‐Ray/bioluminescence Tomography System for Radiation Guidance and Tumor Evaluation
Authors: Shi J , Udayakumar T , Wang Z , Dogan N , Pollack A , Yang Y
Published: July 2016

Purpose:

CT is not able to differentiate tumors from surrounding soft tissue. This study is to develop a bioluminescence tomography (BLT) system that is integrated onto our previously developed CT guided small animal arc radiation treatment system (iSMAART) to guide radiation, monitor tumor growth and evaluate therapeutic response.

Methods:

The BLT system employs a CCD camera coupled with a high speed lens, and is aligned orthogonally to the x‐ray beam central axis. The two imaging modalities, CT and BLT, are physically registered through geometrical calibration. The CT anatomy provides an accurate contour of animal surface which is used to construct 3D mesh for BLT reconstruction. Bioluminescence projections are captured from multiple angles, once every 45 degree rotation. The diffusion equation based on analytical Kirchhoff approximation is adopted to model the photon propagation in tissues. A discrete cosine transform based reweighted L1‐norm regularization (DCT‐re‐L1) algorithm is used for BLT reconstruction. Experiments are conducted on a mouse orthotopic prostate tumor model (n=12) to evaluate the BLT performance, in terms of its robustness and accuracy in locating and quantifying the bioluminescent tumor cells. Iodinated contrast agent was injected intravenously to delineate the tumor in CT. The tumor location and volume obtained from CT also serve as a benchmark against BLT.

Results:

With our cutting edge reconstruction algorithm, BLT is able to accurately reconstruct the orthotopic prostate tumors. The tumor center of mass in BLT is within 0.5 mm radial distance of that in CT. The tumor volume in BLT is significantly correlated with that in CT (R2 = 0.81).

Conclusion:

The BLT can differentiate, localize and quantify tumors. Together with CT, BLT will provide precision radiation guidance and reliable treatment assessment in preclinical cancer research.
TH‐F‐201‐01: The Problem: Is This a Trick Question?
Authors: Bloch C.
Published: July 2016

Multiple choice questions are a tool medical physicists encounter throughout their careers. They are a commonly used method of assessment during our early didactic training (graduate school, residency and board certification). They are used throughout our MOC process both in SAMs and online CE. And they are used for the MOC exam every 10 years. While we have significant training in answering these multiple choice questions, we rarely receive training in how to construct effective multiple choice questions. This is important too, as it is medical physicists who are creating the exams at academic institutions, for the AAPM SAMs and online CE as well as for the ABR exams (both initial and MOC). While there are rigorous scientific methods for evaluating the quality of questions in an exam that has been taken, creating good questions (stem) and multiple choice answers (distractors) requires skill and practice. This talk will cover some of the do's and don'ts for creating good multiple choice questions.

Item analysis of answers to multiple choice questions can reveal a great deal about the quality of the questions. Questions can be measured in terms of their difficulty and ability to discriminate between examinees. The distractors themselves can be evaluated for their ability to discriminate as well. And finally the overall test can be evaluated for reliability. We will discuss some of the specifics of item analysis as well as provide guidelines for constructing good tests items.

Learning Objectives:

Understand rules for writing a good stem

Understand rules for writing good distractors
TH‐F‐201‐02: The Solution: The Science Behind Writing Good Questions
Authors: Richardson S.
Published: July 2016

Multiple choice questions are a tool medical physicists encounter throughout their careers. They are a commonly used method of assessment during our early didactic training (graduate school, residency and board certification). They are used throughout our MOC process both in SAMs and online CE. And they are used for the MOC exam every 10 years. While we have significant training in answering these multiple choice questions, we rarely receive training in how to construct effective multiple choice questions. This is important too, as it is medical physicists who are creating the exams at academic institutions, for the AAPM SAMs and online CE as well as for the ABR exams (both initial and MOC). While there are rigorous scientific methods for evaluating the quality of questions in an exam that has been taken, creating good questions (stem) and multiple choice answers (distractors) requires skill and practice. This talk will cover some of the do's and don'ts for creating good multiple choice questions.

Item analysis of answers to multiple choice questions can reveal a great deal about the quality of the questions. Questions can be measured in terms of their difficulty and ability to discriminate between examinees. The distractors themselves can be evaluated for their ability to discriminate as well. And finally the overall test can be evaluated for reliability. We will discuss some of the specifics of item analysis as well as provide guidelines for constructing good tests items.

Learning Objectives:

Understand rules for writing a good stem

Understand rules for writing good distractors
TH‐F‐202‐00: MRI for Radiation Therapy
Authors: Cai Jing
Published: July 2016

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image‐guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy.

Learning Objectives:

To learn basics of MR physics and understand the differences between various pulse sequences

To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy

Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai
TH‐F‐202‐01: MRI Basics
Authors: Miller W.
Published: July 2016

MRI has excellent soft tissue contrast and can provide both anatomical and physiological information. It is becoming increasingly important in radiation therapy for treatment planning, image‐guided radiation therapy, and treatment assessment. It is critically important at this time point to educate and update our medical physicists about MRI to prepare for the upcoming surge of MRI applications in radiation therapy. This session will review important basics of MR physics, pulse sequence designs, and current radiotherapy application, as well as showcase exciting new developments in MRI that can be potentially useful in radiation therapy.

Learning Objectives:

To learn basics of MR physics and understand the differences between various pulse sequences

To review current applications of MRI in radiation therapy.To discuss recent MRI advances for future MRI guided radiation therapy

Partly supported by NIH (1R21CA165384).; W. Miller, Research supported in part by Siemens Healthcare; G. Li, My clinical research is in part supported by NIH U54CA137788. I have a collaborative research project with Philips Healthcare.; J. Cai, jing cai
Finite difference time domain model of ultrasound propagation in agarose scaffold containing collagen or chondrocytes
Authors: Inkinen Satu I. , Liukkonen Jukka , Malo Markus K. H. , Virén Tuomas , Jurvelin Jukka S. , Töyräs Juha
Published: July 2016

Measurement of ultrasound backscattering is a promising diagnostic technique for arthroscopic evaluation of articular cartilage. However, contribution of collagen and chondrocytes on ultrasound backscattering and speed of sound in cartilage is not fully understood and is experimentally difficult to study. Agarose hydrogels have been used in tissue engineering applications of cartilage. Therefore, the aim of this study was to simulate the propagation of high frequency ultrasound (40 MHz) in agarose scaffolds with varying concentrations of chondrocytes (1 to 32 × 106 cells/ml) and collagen (1.56–200 mg/ml) using transversely isotropic two-dimensional finite difference time domain method (FDTD). Backscatter and speed of sound were evaluated from the simulated pulse-echo and through transmission measurements, respectively. Ultrasound backscatter increased with increasing collagen and chondrocyte concentrations. Furthermore, speed of sound increased with increasing collagen concentration. However, this was not observed with increasing chondrocyte concentrations. The present study suggests that the FDTD method may have some applicability in simulations of ultrasound scattering and propagation in constructs containing collagen and chondrocytes. Findings of this study indicate the significant role of collagen and chondrocytes as ultrasound scatterers and can aid in development of modeling approaches for understanding how cartilage architecture affects to the propagation of high frequency ultrasound.
Predictive biomarkers for HDAC inhibitor efficacy
Authors: Ferrarelli Leslie K.
Published: July 2016

High abundance of the E3 ligase FBW7 may predict therapeutic efficacy of HDAC inhibitors in ΔNp63-positive tumors.
Early prediction of typical outcome and mild developmental delay for prioritisation of service delivery for very preterm and very low birthweight infants: a study protocol
Authors: Caesar Rebecca , Boyd Roslyn N , Colditz Paul , Cioni Giovani , Ware Robert S , Salthouse Kaye , Doherty Julie , Jackson Maxine , Matthews Leanne , Hurley Tom , Morosini Anthony , Thomas Clare , Camadoo Laxmi , Baer Erica
Published: July 2016

Introduction

Over 80% of very preterm (<32 weeks) and very low birthweight (<1500 g) infants will have either typical development (TD) or mild developmental delay (MDD) in multiple domains. As differentiation between TD and MDD can be difficult, infants with MDD often miss opportunities for intervention. For many clinicians, the ongoing challenge is early detection of MDD without over servicing the population. This study aims to: (1) identify early clinical biomarkers for use in this population to predict and differentiate between TD and MDD at 24 months corrected age. (2) Determine the extent to which family and caregiver factors will contribute to neurodevelopmental and behavioural outcomes.

Methods and analysis

Participants will be a prospective cohort of 90 infants (<32 weeks and/or <1500 g). Between 34 weeks gestational age and 16 weeks post-term, infants will have a series of 5 neurological, neuromotor, neurobehavioural and perceptual assessments including General Movement Assessment at preterm, writhing and fidgety age. Primary caregivers will complete questionnaires to identify social risk, maternal depression and family strain. Extensive perinatal data will be collected from the medical record. At 24 months, corrected age (c.a) infants will be assessed using standardised tools including the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley III). Longitudinal trajectories of early assessment findings will be examined to determine any predictive relationship with motor and cognitive outcomes at 24 months c.a. Published data of a cohort of Australian children assessed with the Bayley III at 24 months c.a will provide a reference group of term-born controls.

Ethics

Ethical approval has been obtained from the Queensland Children's Health Services Human Research Ethics Committee (HREC/13/QRCH/66), the University of Queensland (2013001019) and the Sunshine Coast Hospital and Health Service, SC-Research Governance (SSA/13/QNB/66). Publication of all study outcomes will be in peer-reviewed journals.

Trial registration number

ACTRN12614000480684; Pre-results.
Diagnosis and mortality in prehospital emergency patients transported to hospital: a population-based and registry-based cohort study
Authors: Christensen Erika Frischknecht , Larsen Thomas Mulvad , Jensen Flemming Bøgh , Bendtsen Mette Dahl , Hansen Poul Anders , Johnsen Søren Paaske , Christiansen Christian Fynbo
Published: July 2016

Objective

Knowledge about patients after calling for an ambulance is limited to subgroups, such as patients with cardiac arrest, myocardial infarction, trauma and stroke, while population-based studies including all diagnoses are few. We examined the diagnostic pattern and mortality among all patients brought to hospital by ambulance after emergency calls.

Design

Registry-based cohort study.

Setting and participants

We included patients brought to hospital in an ambulance dispatched after emergency calls during 2007–2014 in the North Denmark Region (580 000 inhabitants). We reported hospital diagnosis according to the chapters of the International Classification of Diseases, 10th Edition (ICD-10), and studied death on days 1 and 30 after the call. Cohort characteristics and diagnoses were described, and the Kaplan-Meier method was used to estimate mortality and 95% CIs.

Results

In total, 148 757 patients were included, mean age 52.9 (SD 24.3) years. The most frequent ICD-10 diagnosis chapters were: ‘injury and poisoning’ (30.0%), and the 2 non-specific diagnosis chapters: ‘symptoms and abnormal findings, not elsewhere classified’ (17.5%) and ‘factors influencing health status and contact with health services’ (14.1%), followed by ‘diseases of the circulatory system’ (10.6%) and ‘diseases of the respiratory system’ (6.7%). The overall 1-day mortality was 1.8% (CI 1.7% to 1.8%) and 30-day mortality 4.7% (CI 4.6% to 4.8%). ‘Diseases of the circulatory system’ had the highest 1-day mortality of 7.7% (CI 7.3% to 8.1%) accounting for 1209 deaths. After 30 days, the highest number of deaths were among circulatory diseases (2313), respiratory diseases (1148), ‘symptoms and abnormal findings, not elsewhere classified’ (1119) and ‘injury and poisoning’ (741), and 30 days mortality in percentage was 14.7%, 11.6%, 4.3% and 1.7%, respectively.

Conclusions

Patients' diagnoses from hospital stay after calling 1-1-2 in this population-based study were distributed across all ICD-10 chapters. Mortality varied widely between diagnostic groups. Non-specific diagnoses accounted for one-third of the patients and contributed to mortality in terms of total number of deaths.
Epidemiology of major depressive disorder in South Africa (1997–2015): a systematic review protocol
Authors: Nglazi Mweete D , Joubert Jané D , Stein Dan J , Lund Crick , Wiysonge Charles S , Vos Theo , Pillay-van Wyk Victoria , Roomaney Rifqah A , Muhwava Lorrein S , Bradshaw Debbie
Published: July 2016

Introduction

Major depressive disorder (MDD) is a leading cause of disease and disability globally and in South Africa. Epidemiological data for MDD are essential to estimate the overall disease burden in a country. The objective of the systematic review is to examine the evidence base for prevalence, incidence, remission, duration, severity, case fatality and excess mortality of MDD in South Africa from 1997 to 2015.

Methods and analysis

We will perform electronic searches in PubMed, PsycINFO, Scopus and other bibliographical databases. Articles published between January 1997 and December 2015 will be eligible for inclusion in this review. The primary outcomes will be prevalence, incidence, remission, duration, severity, case fatality and excess mortality of MDD. The secondary outcomes will be risk factors and selected populations for MDD. If appropriate, a meta-analysis will be performed. If a meta-analysis is not possible, the review findings will be presented narratively and in tables. Subgroup analyses will be conducted with subgroups defined by population group, rural/urban settings and study designs, if sufficient data are available.

Ethics and dissemination

The systematic review will use published data that are not linked to individuals. The review findings may have implications for future research prioritisation and disease modelling of MDD to estimate its morbidity burden in South Africa, and will be disseminated electronically and in print through peer-reviewed publications.

Trial Registration number:

International Prospective Register of Systematic Reviews (PROSPERO) CRD42015024885.
Mepivacaine attenuates vasodilation induced by ATP-sensitive potassium channels in rat aorta
Authors: Baik Jiseok , Ok Seong-Ho , Kim Eun-Jin , Kang Dawon , Hong Jeong-Min , Shin Il-Woo , Lee Heon Keun , Chung Young-Kyun , Cho Youngil , Lee Soo Hee , Kang Sebin , Sohn Ju-Tae
Published: July 2016

The goal of this in vitro study was to investigate the effect of mepivacaine on vasodilation induced by the ATP-sensitive potassium (KATP) channel opener levcromakalim in isolated endothelium-denuded rat aortas. The effects of mepivacaine and the KATP channel inhibitor glibenclamide, alone or in combination, on levcromakalim-induced vasodilation were assessed in the isolated aortas. The effects of mepivacaine or combined treatment with a protein kinase C (PKC) inhibitor, GF109203X, and mepivacaine on this vasodilation were also investigated. Levcromakalim concentration–response curves were generated for isolated aortas precontracted with phenylephrine or a PKC activator, phorbol 12,13-dibutyrate (PDBu). Further, the effects of mepivacaine and glibenclamide on levcromakalim-induced hyperpolarization were assessed in rat aortic vascular smooth muscle cells. Mepivacaine attenuated levcromakalim-induced vasodilation, whereas it had no effect on this vasodilation in isolated aortas pretreated with glibenclamide. Combined treatment with GF109203X and mepivacaine enhanced levcromakalim-induced vasodilation compared with pretreatment with mepivacaine alone. This vasodilation was attenuated in aortas precontracted with PDBu compared with those precontracted with phenylephrine. Mepivacaine and glibenclamide, alone or in combination, attenuated levcromakalim-induced membrane hyperpolarization. Taken together, these results suggest that mepivacaine attenuates vasodilation induced by KATP channels, which appears to be partly mediated by PKC.
LIQUIDITY RISK AND INSTABILITIES IN PORTFOLIO OPTIMIZATION
Authors: CACCIOLI FABIO , KONDOR IMRE , MARSILI MATTEO , STILL SUSANNE
Published: July 2016

We show that including a term which accounts for finite liquidity in portfolio optimization naturally mitigates the instabilities that arise in the estimation of coherent risk measures on finite samples. This is because taking into account the impact of trading in the market is mathematically equivalent to introducing a regularization on the risk measure. We show here that the impact function determines which regularizer is to be used. We also show that any regularizer based on the norm [Formula: see text] with [Formula: see text] makes the sensitivity of coherent risk measures to estimation error disappear, while regularizers with [Formula: see text] do not. The [Formula: see text] norm represents a border case: its “soft” implementation does not remove the instability, but rather shifts its locus, whereas its “hard” implementation (including hard limits or a ban on short selling) eliminates it. We demonstrate these effects on the important special case of expected shortfall (ES) which has recently become the global regulatory market risk measure.
Market Efficiency and Arbitrage Opportunities for Russian Depositary Receipts Cross-Listed on the London Stock Exchange
Authors: Kim Oksana
Published: July 2016

This study examines the Russian stock market efficiency from two perspectives. First, we document that for the sample of Russian firms cross-listed on the Main Market of the London Stock Exchange (LSE) as Global Depositary Receipts (GDRs), the return series obtained from both the local market and the LSE are time-invariant and hence, predictable. This suggests that the market is inefficient with respect to pricing Russian GDRs and that investors are likely to make systematic nonzero profits. Second, we document profitable arbitrage opportunity surrounding the announcement to adopt IFRS, which is an additional evidence of market inefficiency. The significant pricing spread observed on this key date was due to the differential market reaction to IFRS adoption — neutral on the local MICEX exchange dominated by individual traders and significantly negative on the LSE dominated by institutional investors. This finding can be explained by (i) informational advantages of the local investors due to geographic proximity, (ii) differential expectations with respect to governance norms and listing requirements, and (iii) difference in portfolio composition of the two investor groups.
Ultimate Controlling Shareholders and Dividend Payout Policy in Chinese Stock Market
Authors: Guo Jianan
Published: July 2016

Departing from the traditional cash flow rights-dividend policy framework, this study investigates whether the level of control rights and the types of ultimate controlling shareholders (UCSs) of listed firms in China influence their cash dividend payout. We find that the level of control rights is positively associated with both the probability to pay and the level of cash dividend payout, which indicates that UCSs use cash dividends to reduce the agency cost of free cash flow and redirect listed firms’ cash balance. Furthermore, different types of UCSs influence dissimilarly on the controlled firms’ cash dividends, which can be attributed to the backgrounds of these UCSs originating from China’s unique partial share issuance privatization process.
Bounded Repairability for Regular Tree Languages
Authors: Bourhis Pierre , Puppis Gabriele , Riveros Cristian , Staworko Sławek
Published: July 2016

We study the problem of bounded repairability of a given restriction tree language
R
into a target tree language
T
. More precisely, we say that
R
is bounded repairable with respect to
T
if there exists a bound on the number of standard tree editing operations necessary to apply to any tree in
R
to obtain a tree in
T
. We consider a number of possible specifications for tree languages: bottom-up tree automata (on curry encoding of unranked trees) that capture the class of XML schemas and document type definitions (DTDs). We also consider a special case when the restriction language
R
is universal (i.e., contains all trees over a given alphabet).

We give an effective characterization of bounded repairability between pairs of tree languages represented with automata. This characterization introduces two tools—synopsis trees and a coverage relation between them—allowing one to reason about tree languages that undergo a bounded number of editing operations. We then employ this characterization to provide upper bounds to the complexity of deciding bounded repairability and show that these bounds are tight. In particular, when the input tree languages are specified with arbitrary bottom-up automata, the problem is coNExp-complete. The problem remains coNExp-complete even if we use deterministic nonrecursive DTDs to specify the input languages. The complexity of the problem can be reduced if we assume that the alphabet, the set of node labels, is fixed: the problem becomes PS
pace
-complete for nonrecursive DTDs and coNP-complete for deterministic nonrecursive DTDs. Finally, when the restriction tree language
R
is universal, we show that the bounded repairability problem becomes E
xp
-complete if the target language is specified by an arbitrary bottom-up tree automaton and becomes tractable (P-complete, in fact) when a deterministic bottom-up automaton is used.
BlueDBM
Authors: Jun Sang-Woo , Liu Ming , Lee Sungjin , Hicks Jamey , Ankcorn John , King Myron , Xu Shuotao , Arvind
Published: July 2016

Complex data queries, because of their need for random accesses, have proven to be slow unless all the data can be accommodated in DRAM. There are many domains, such as genomics, geological data, and daily Twitter feeds, where the datasets of interest are 5TB to 20TB. For such a dataset, one would need a cluster with 100 servers, each with 128GB to 256GB of DRAM, to accommodate all the data in DRAM. On the other hand, such datasets could be stored easily in the flash memory of a rack-sized cluster. Flash storage has much better random access performance than hard disks, which makes it desirable for analytics workloads. However, currently available off-the-shelf flash storage packaged as SSDs does not make effective use of flash storage because it incurs a great amount of additional overhead during flash device management and network access. In this article, we present BlueDBM, a new system architecture that has flash-based storage with in-store processing capability and a low-latency high-throughput intercontroller network between storage devices. We show that BlueDBM outperforms a flash-based system without these features by a factor of 10 for some important applications. While the performance of a DRAM-centric system falls sharply even if only 5% to 10% of the references are to secondary storage, this sharp performance degradation is not an issue in BlueDBM. BlueDBM presents an attractive point in the cost/performance tradeoff for Big Data analytics.
Monadic Datalog and Regular Tree Pattern Queries
Authors: Mazowiecki Filip , Murlak Filip , Witkowski Adam
Published: July 2016

Containment of monadic datalog programs over trees is decidable. The situation is more complex when tree nodes carry labels from an infinite alphabet that can be tested for equality. It then matters whether the descendant relation is allowed or not: the descendant relation can be eliminated easily from monadic programs only when label equalities are not used. With descendant, even containment of linear monadic programs in unions of conjunctive queries is undecidable, and positive results are known only for bounded-depth trees.

We show that without descendant, containment of connected monadic programs is decidable over ranked trees, but over unranked trees it is so only for linear programs. With descendant, it becomes decidable over unranked trees under restriction to downward programs: each rule only moves down from the node in the head. This restriction is motivated by regular tree pattern queries, a recent formalism in the area of ActiveXML, which we show to be equivalent to linear downward programs.
Diminished Control in Crowdsourcing
Authors: Gould Sandy J. J. , Cox Anna L. , Brumby Duncan P.
Published: July 2016

Obtaining high-quality data from crowds can be difficult if contributors do not give tasks sufficient attention. Attention checks are often used to mitigate this problem, but, because the roots of inattention are poorly understood, checks often compel attentive contributors to complete unnecessary work. We investigated a potential source of inattentiveness during crowdwork: multitasking. We found that workers switched to other tasks every 5 minutes, on average. There were indications that increasing switch frequency negatively affected performance. To address this, we tested an intervention that encouraged workers to stay focused on our task after multitasking was detected. We found that our intervention reduced the frequency of task switching. It also improves on existing attention checks because it does not place additional demands on workers who are already focused. Our approach shows that crowds can help to overcome some of the limitations of laboratory studies by affording access to naturalistic multitasking behavior.