Comparison of two mycobacterial strains in performance of the whole blood mycobacterial growth inhibition assay in Indian children.

A major challenge in tuberculosis is identifying correlates of a protective immune response. The Mycobacterial Growth Inhibition Assay (MGIA) is a functional assay providing an integrated measure of the host immune response to mycobacteria. However, its feasibility is limited by reliance on biosafety level 3 facilities, and its performance has not been widely evaluated in TB-endemic settings. Here, we compared two mycobacterial strains (M. tuberculosis H37Rv versus attenuated M. bovis BCG) in the performance of whole-blood MGIA in 30 TB-exposed children (median age 2 years) in Chennai, India. The time-to-positivity in both assays was similar (5.7 days vs 6 days) and the mycobacterial growth of M. tuberculosis H37Rv and M. bovis BCG were correlated (r = 0.64, p<0.0001). In Bland-Altman analysis, the bias was -0.54 days (95% limit of agreement -2.08, 0.99). Collectively, our results indicate that M. tuberculosis H37Rv can be substituted with the less virulent M. bovis BCG strain to improve feasibility of the MGIA assay, particularly in low-income settings.

A multi-institutional evaluation of small field output factor determination following the recommendations of IAEA/AAPM TRS-483.

PURPOSE: The aim of this work was to test the implementation of small field dosimetry following TRS-483 and to develop quality assurance procedures for the experimental determination of small field output factors (SFOFs). MATERIALS AND METHODS: Twelve different centers provided SFOFs determined with various detectors. Various linac models using the beam qualities 6 MV and 10 MV with flattening filter and without flattening filter were utilized to generate square fields down to a nominal field size of 0.5 cm × 0.5 cm. The detectors were positioned at 10 cm depth in water. Depending on the local situation, the source-to-surface distance was either set to 90 cm or 100 cm. The SFOFs were normalized to the output of the 10 cm × 10 cm field. The spread of SFOFs measured with different detectors was investigated for each individual linac beam quality and field size. Additionally, linac-type specific SFOF curves were determined for each beam quality and the SFOFs determined using individual detectors were compared to these curves. Example uncertainty budgets were established for a solid state detector and a micro ionization chamber. RESULTS: The spread of SFOFs for each linac and field was below 5% for all field sizes. With the exception of one linac-type, the SFOFs of all investigated detectors agreed within 10% with the respective linac-type SFOF curve, indicating a potential inter-detector and inter-linac variability. CONCLUSION: Quality assurance on the SFOF measurements can be done by investigation of the spread of SFOFs measured with multiple detectors and by comparison to linac-type specific SFOFs. A follow-up of a measurement session should be conducted if the spread of SFOFs is larger than 5%, 3%, and 2% for field sizes of 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 2 cm × 2 cm, respectively. Additionally, deviations of measured SFOFs to the linac-type-curves of more than 7%, 3%, and 2% for field sizes 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 1 cm × 1 cm, respectively, should be followed up.

A non-invasive acoustic-trapping of zebrafish microfluidics.

Zebrafish is an emerging alternative model in behavioral and neurological studies for pharmaceutical applications. However, little is known regarding the effects of noise exposure on laboratory-grown zebrafish. Accordingly, this study commenced by exposing zebrafish embryos to loud background noise (≥200 Hz, 80 ± 10 dB) for five days in a microfluidic environment. The noise exposure was found to affect the larvae hatching rate, larvae length, and swimming performance. A microfluidic platform was then developed for the sorting/trapping of hatched zebrafish larvae using a non-invasive method based on light cues and acoustic actuation. The experimental results showed that the proposed method enabled zebrafish larvae to be transported and sorted into specific chambers of the microchannel network in the desired time frame. The proposed non-invasive trapping method thus has potentially profound applications in drug screening.

Comparing Setup Errors Using Portal Imaging in Patients With Gynecologic Cancers by Two Methods of Alignment.

AIMS: Alignment tattoos on a lax abdomen contribute to misalignment of patients undergoing abdomino-pelvic radiotherapy (RT). The present study was undertaken to assess setup reproducibility in gynecologic cancer patients positioned identically but aligned for treatment to machine isocenter by two different ways. MATERIALS AND METHODS: A prospective study in 35 women treated with radical RT for gynecologic malignancy was undertaken. A RT planning contrast-enhanced computed tomography scan in the supine position using an foot and ankle positioning device was done, and three reference points tattooed on the reference plane, anteriorly at the mons pubis and one on each side laterally at a fixed table top-to-vertical height of 10 cm, whereas a fourth point was tattooed at the xiphoid in the anterior midline. Patients were aligned using either a field center, that is, conventional method (Arm I, n = 18) or by a new setup isocenter (Arm II, n = 17) defined by a cranial offset of 4 cm to the reference plane for daily treatment. Anterior and right lateral digitally reconstructed radiograph setup fields were created at the treatment isocenters and compared with orthogonal megavoltage portal images (PI) taken during initial 3 days of RT and subsequently twice weekly. Setup deviations-rotations and translations were analysed in mediolateral (ML), craniocaudal, and anteroposterior direction. No online and offline corrections were performed. Population systematic error and random error were calculated and planning target volume margins required were estimated using van Herk's formula. RESULTS: Arm I had 209 PI while Arm II had 188 PI. Patients in arm II had a lesser systematic error in the ML direction. Patients with large pelvic girth (>95 cm) were susceptible for greater movements during treatment, more so in Arm I, major shifts (>5 mm) with respect to Arm II in the ML direction (37% vs. 22%, P = .001). A larger planning target volume expansion was required in Arm I (1.6 cm) compared with Arm II (0.9 cm). The margin expansion required from clinical target volume in anteroposterior direction was about 0.6 cm and about a cm in the craniocaudal direction in both the arm. CONCLUSIONS: Alignment of patient with anterior tattoo at the relatively immobile portion of lower abdomen (mons pubis) Arm II (setup) is superior to a more cranial location over the flabby abdomen during radiation treatment.

A Shape Memory Alloy-Based Miniaturized Actuator for Catheter Interventions.

In the current scenario of endovascular intervention, surgeons have to manually navigate the catheter within the complex vasculature of the human body under the guidance of X-ray. This manual intervention upsurges the possibilities of vessel damage due to frequent contact between the catheter and vasculature wall. In this context, a shape memory alloy-based miniaturized actuator was proposed in this study with a specific aim to reduce vessel wall related damage by improving the bending motions of the guidewire tip in a semi-automatic fashion. The miniaturized actuator was integrated with a FDA-approved guidewire and tested within a patient-specific vascular network model to realize its feasibility in the real surgical environment. The results illustrate that the miniaturized actuator gives a bending angle over 23° and lateral displacement over 900 µm to the guide wire tip by which the guidewire can be navigated with precision and possible vessel damage during the catheter intervention can certainly be minimized. In addition to it, the dynamic responses of the presented actuator were further investigated through numerical simulation in conjunction with the analytic analysis.

A noninvasive light driven technique integrated microfluidics for zebrafish larvae transportation.

Transferring the zebrafish larvae on an imaging platform has long been performed manually by the use of forceps or through mechanical pumping. These methods induce detrimental damages to the fragile bodies of zebrafish larvae during the transportation. To address this issue, in this work we are devising a light driven technique to transport zebrafish larvae within a microfluidic environment. In particular, an optomotor behavioral response of the zebrafish larvae was controlled through the computer animated moving gratings for their transportation within a microfluidics chamber. It was observed that with an optimum grating frequency of 1.5 Hz and a grating width ratio of 1:1, a 5 days-post fertilization zebrafish larva can be transported within minimum and maximum time periods of 0.63 and 2.49 s, respectively. This proposed technique can be utilized towards multi-automatic transportation of zebrafish larvae within the microfluidic environment as well as the zebrafish core facility.

Influence of jaw tracking in intensity-modulated and volumetric-modulated arc radiotherapy for head and neck cancers: a dosimetric study.

PURPOSE: To Study the dosimetric advantage of the Jaw tracking technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for Head and Neck Cancers. MATERIALS AND METHODS: We retrospectively selected 10 previously treated head and neck cancer patients stage (T1/T2, N1, M0) in this study. All the patients were planned for IMRT and VMAT with simultaneous integrated boost technique. IMRT and VMAT plans were performed with jaw tracking (JT) and with static jaw (SJ) technique by keeping the same constraints and priorities for a particular patient. Target conformity, dose to the critical structures and low dose volumes were recorded and analyzed for IMRT and VMAT plans with and without JT for all the patients. RESULTS: The conformity index average of all patients followed by standard deviation ([Formula: see text] ± [Formula: see text]) of the JT-IMRT, SJ-IMRT, JT-VMAT, and SJ-VMAT were 1.72 ± 0.56, 1.67 ± 0.57, 1.83 ± 0.65, and 1.85 ± 0.64, and homogeneity index were 0.059 ± 0.05, 0.064 ± 0.05, 0.064 ± 0.04, and 0.064 ± 0.05. JT-IMRT shows significant mean reduction in right parotid and left parotid shows of 7.64% (p < 0.001) and 7.45% (p < 0.001) compare to SJ-IMRT. JT-IMRT plans also shows considerable dose reduction to thyroid, inferior constrictors, spinal cord and brainstem compared to the SJ-IMRT plans. CONCLUSION: Significant dose reductions were observed for critical structure in the JT-IMRT compared to SJ-IMRT technique. In JT-VMAT plans dose reduction to the critical structure were not significant compared to the SJ-IMRT due to relatively lesser monitor units.

Manipulation of zebrafish's orientation using artificial cilia in a microchannel with actively adaptive wall design.

The zebrafish is a powerful genetic model organism especially in the biomedical chapter for new drug discovery and development. The genetic toolbox which this vertebrate possesses opens a new window to investigate the etiology of human diseases with a high degree genetic similarity. Still, the requirements of laborious and time-consuming of contemporary zebrafish processing assays limit the procedure in carrying out such genetic screen at high throughput. Here, a zebrafish control scheme was initiated which includes the design and validation of a microfluidic platform to significantly increase the throughput and performance of zebrafish larvae manipulation using the concept of artificial cilia actuation. A moving wall design was integrated into this microfluidic platform first time in literature to accommodate zebrafish inside the microchannel from 1 day post-fertilization (dpf) to 6 dpf and can be further extended to 9 dpf for axial orientation control in a rotational range between 0 to 25 degrees at the minimum step of 2-degree increment in a stepwise manner. This moving wall feature was performed through the deflection of shape memory alloy wire embedded inside the microchannel controlled by the electrical waveforms with high accuracy.

Endoleak Assessment Using Computational Fluid Dynamics and Image Processing Methods in Stented Abdominal Aortic Aneurysm Models.

Endovascular aortic aneurysm repair (EVAR) is a predominant surgical procedure to reduce the risk of aneurysm rupture in abdominal aortic aneurysm (AAA) patients. Endoleak formation, which eventually requires additional surgical reoperation, is a major EVAR complication. Understanding the etiology and evolution of endoleak from the hemodynamic perspective is crucial to advancing the current posttreatments for AAA patients who underwent EVAR. Therefore, a comprehensive flow assessment was performed to investigate the relationship between endoleak and its surrounding pathological flow fields through computational fluid dynamics and image processing. Six patient-specific models were reconstructed, and the associated hemodynamics in these models was quantified three-dimensionally to calculate wall stress. To provide a high degree of clinical relevance, the mechanical stress distribution calculated from the models was compared with the endoleak positions identified from the computed tomography images of patients through a series of imaging processing methods. An endoleak possibly forms in a location with high local wall stress. An improved stent graft (SG) structure is conceived accordingly by increasing the mechanical strength of the SG at peak wall stress locations. The presented analytical paradigm, as well as numerical analysis using patient-specific models, may be extended to other common human cardiovascular surgeries.

Microscale flow propulsion through bioinspired and magnetically actuated artificial cilia.

Recent advances in microscale flow propulsion through bioinspired artificial cilia provide a promising alternative for lab-on-a-chip applications. However, the ability of actuating artificial cilia to achieve a time-dependent local flow control with high accuracy together with the elegance of full integration into the biocompatible microfluidic platforms remains remote. Driven by this motive, the current work has constructed a series of artificial cilia inside a microchannel to facilitate the time-dependent flow propulsion through artificial cilia actuation with high-speed (>40 Hz) circular beating behavior. The generated flow was quantified using micro-particle image velocimetry and particle tracking with instantaneous net flow velocity of up to 10(1 ) µm/s. Induced flow patterns caused by the tilted conical motion of artificial cilia constitutes efficient fluid propulsion at microscale. This flow phenomenon was further measured and illustrated by examining the induced flow behavior across the depth of the microchannel to provide a global view of the underlying flow propulsion mechanism. The presented analytic paradigms and substantial flow evidence present novel insights into the area of flow manipulation at microscale.

Investigating the effect of dose rate and maximum allowable MLC leaf velocity in dynamic IMRT.

The purpose of this study is to analyze the effect of various dose rates (DR) and maximum allowable MLC leaf velocities (MLV) in dynamic Intensity Modulated Radiotherapy (IMRT) planning and delivery of head and neck patients. Five head and neck patients were retrospectively included in this study. The initial dynamic IMRT 'reference plans' were created for all these patients, using a DR of 400 MU/min and MLV of 2.5 cm/s. Additional plans were generated by varying the DR and MLV values. The DR value was varied from 100 to 600 MU/min, in increments of 100 MU/min, for a MLV of 2.5 cm/s. Also the MLV was varied from 0.5 to 3 cm/s, in increments of 0.5 cm, for a DR of 400 MU/min. In order to maintain the prescribed dose to the PTV, the DR was allowed to vary ('beam hold or DR modulation' during delivery) when the MLV was changed and the MLV was allowed to vary when the DR was changed. The mean doses to the PTV as well as parotids, maximum dose of spinal cord and total MU were recorded for analysis. The effect of DR and MLV on treatment delivery was analyzed using the portal dosimetry for all the above plans. The predicted portal dose fluences of the TPS were compared with the measured EPID fluences using gamma evaluation criteria of 2% dose difference and 2 mm distance to agreement. A small proportional increase in OAR doses with DR was observed. Increases to MLV value resulted in decreases of the OAR doses and this effect was considerable for values below 1.5 cm/s. DR and MLV both resulted in no appreciable dose variation to the target. The total MU to deliver the plan increases with increasing DR and decreasing MLV. When comparing portal images derived from the treatment plans with portal images obtained by delivering the treatments, it was observed that the treatments was most reliably delivered when the DRs were set to lower values and when the MLVs were set to higher values.

Dosimetric effect of multileaf collimator leaf width in intensity-modulated radiotherapy delivery techniques for small- and large-volume targets.

The purpose of this study was to evaluate the dosimetric effect of the leaf width of a multileaf collimator (MLC) in intensity-modulated radiotherapy (IMRT) delivery techniques for small- and large-volume targets. We retrospectively selected previously treated 5 intracranial and 5 head-neck patients for this study to represent small- (range, 18.37-72.75 cc; mean, 42.99 cc) and large-volume (range, 312.31-472.84 cc; mean, 361.14 cc) targets. A 6-MV photon beam data was configured for Brianlab m3 (3 mm), Varian Millennium 120 (5 mm) and Millennium 80 (10 mm) MLCs in the Eclipse treatment-planning system. Sliding window and step-shoot IMRT plans were generated for intracranial patients using all the above-mentioned MLCs; but due to the field size limitation of Brainlab MLC, we used only 5-mm and 10-mm MLCs in the head-and-neck patients. Target conformity, dose to the critical organs and dose to normal tissues were recorded and evaluated. Although the 3-mm MLC resulted in better target conformity (mean difference of 7.7% over 5-mm MLC and 12.7% over 10-mm MLC) over other MLCs for small-volume targets, it increased the total monitor units of the plans. No appreciable differences in terms of target conformity, organ at risk and normal-tissue sparing were observed between the 5-mm and 10-mm MLCs for large-volume targets. The effect of MLC leaf width was not quantifiably different in sliding window and step and shoot techniques. In addition, we observed that there was no additional benefit to the sliding-window (SW) technique when compared to the step-shoot (SS) technique as a result of reduction of MLC leaf width.

Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas.

PURPOSE: The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). METHODS AND MATERIALS: Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. RESULTS: Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins >55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. CONCLUSION: Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.