Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 30 Ιουνίου 2016
A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma
Abstract
Background
Robatumumab (19D12; MK-7454 otherwise known as SCH717454) is a fully human antibody that binds to and inhibits insulin-like growth factor receptor-1 (IGF-1R). This multiinstitutional study (P04720) determined the safety and clinical efficacy of robatumumab in three separate patient groups with resectable osteosarcoma metastases (Group 1), unresectable osteosarcoma metastases (Group 2), and Ewing sarcoma metastases (Group 3).
Procedure
Robatumumab infusions were administered every 2 weeks and were well tolerated with minimal toxicity. Centrally reviewed response data were available for 144 patients.
Results
Low disease burden was important for osteosarcoma response: three of 31 patients had complete response or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) in resectable patients (Group 1) versus zero of 29 in unresectable patients (Group 2); median overall survival was 20 months in Group 1 versus 8.2 months in Group 2. In centrally reviewed patients with Ewing sarcoma with PET-CT data (N = 84/115), there were six PR, 23 stable disease, and 55 progression of disease by RECIST at 2 months. Patients with Ewing sarcoma had a median overall survival of 6.9 months. However, responding patients with Ewing sarcoma were allowed to continue on treatment after study closure. A minority of patients with metastatic Ewing sarcoma showed clinical responses and have remained healthy after receiving 25–115 doses of robatumumab with remissions of >4 years duration (N = 6).
Conclusions
These findings show that although the IGF-1R remains an attractive treatment target, additional research is needed to identify responders and/or means to achieve durable remissions in order to successfully exploit IGF-1R signal blockade in Ewing sarcoma (clinicaltrials.gov: NCT00617890).
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Abhidharma in China: reflections on 'Matching meanings' and Xuanxue
This chapter of the volume "Tekst, History, and Philosophy. Abhidharma across Buddhist Scholastic Traditions" discusses the phenomenon of 'Matching Meanings' (Geyi), a technique allegedly used to translate Indian and Central Asian Buddhist Texts into Chinese. Building on previous scholarship, this article formulates a new hypothesis: rather than interpreting 'Geyi' as a technique to make Abhidharma Texts understandable and palatable for the Chinese audience, this article suggests that 'Geyi' should rather be seen as a Neo-Confucian technique to rally Chinese intellectuals under the umbrella of 'Confucianism' after the disunity of the empire of the third to sixth centuries.
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Appearances of Dawla and Political Order in late medieval Syro-Egypt. The state, social theory, and the political history of the Cairo Sultanate (thirteenth-sixteenth centuries)
This paper is a reflexive essay that re-imagines the historical agency of what traditionally tends to be subsumed under the phenomenon of the Mamluk state. It is argued that the notions of state in modern research and of dawla in contemporary texts remain an issue of related analytical confusion. Engaging with this confusion in the generalising fashion of a historical sociology of late medieval Syro-Egyptian political action, this essay proposes an alternative analytical model that is inspired by Michael Chamberlain's prioritisation of social practices of household reproduction and by Timothy Mitchell's related understanding of the state as a structural effect of practices of social differentiation. The proposed model sees sultanic political order —the state— as process, in constant flux as the structural effect and structuring embodiment of constantly changing practices of social reproduction, of elite integration and of political distinction, in contexts that range between multipolar and unipolar social organisation at and around Cairo's court and its military elites. The essay ends with summarily suggesting from this model how the socio-culturally structured and structuring memories of dynastic political order that had remained politically dominant for most of the thirteenth and fourteenth centuries were all but obliterated in the fifteenth century by a new layer of particularly 'Mamluk' socio-political meaning.
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Abhidharma as rational inquiry
This introductory article to the volume "Tekst, History, and Philosophy. Abhidharma across Buddhist Scholastic Traditions" discusses how the Abhidharma genre of Buddhist literature can be interpreted as the result of philosophical debate with, for orginal Indian Buddhism, different indigenous and foreign philosophies and religions. The Abhidharma genre as such is the product of historical and philosophical development.
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Voice symptoms and risk factors for developing voice disorders in future musical actors
Musical theater students follow an intensive program of singing, acting and physical excercises (dancing) and are expected to participate in long rehearsals and full performances. As they are absolutely depending on their vocal quality and vocal capacities for their studies and their future profession, an optimal voice coaching is very important. The purpose of this study was to determine the voice quality, voice symptoms and the risk factors for developing voice problems in future elite vocal performers (musical theater performers). Thirty-one Musical students (7 men and 24 women) with a mean age of 20 years participated to the study. To determine the objective voice quality aerodynamic measurements, voice range profile, acoustic analysis and Dysphonia Severity Index were used. To inventory the voice symptoms and the risk factors for developing voice disorders the Dutch version of the checklists (De Bodt et al. 2008) of Russel et al. (2000) were used. The questionnaires investigate the presence and the frequency (never, daily, weekly, monthly) of voice symptoms and risk factors (vocal abuse, vocal misuse) as reported by the subjects. Psychosocial impact of a voice disorder was investigated using the the Voice Handicap Index and Singing Voice Handicap Index. The mean DSI in male and female Musical theater students was respectively 3.9 and 5.6, both corresponding with an overall good vocal quality. The results of the VHI showed no important psychosocial impact on the speaking voice. Despite the overall good vocal quality, more than 40% experienced voice symptoms on a regular basis. Vocal misuse and abuse was also frequently reported. Videolaryngostroboscopy revealed a high presence of organic and functional voice disorders. Note: The objective vocal quality in this group was presented in a poster at the voice conference in Philadelphia in 2015. This presentation focuses on new data regarding the symptoms and risk factors reported by the subjects.
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El espacio narrativo en la novela chilena postdictatorial. Casas habitadas
In El espacio narrativo en la novela chilena postdictatorial, Bieke Willem undertakes an analysis of the representation of space to identify a change in the poetics of recent fiction in Chile. Through a series of close readings of eight novels by some of Chile's most influential contemporary writers (Eltit, Marín, Bolaño, Fernández, Zambra and Zúñiga), she examines how Chilean authors in the period following the dictatorship deal in a melancholic or nostalgic way with the recent past and with changes in the meaning of space. The book combines reflections on literature, sociology, architecture and urbanism to paint a picture of what it means for these authors to be living in contemporary Chile.
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The impact of a theater performance on the vocal quality of actors
Background: Theater actors are a special group of elite vocal performers where the slightest vocal difficulty can have serious professional consequences. Little is known about the presence of vocal complaints and dysphonia in this group. Aims: The purpose of this study was to investigate vocal quality, vocal complaints and risk factors for developing voice disorders in theater actors. Secondly, the impact of one vocal performance on the voice was investigated by comparing objective and subjective voice quality immediately before and after a theater performance of one and a half hour. Methods and procedures: Speech samples of 26 theater actors (15 men, 11 women) with a mean age of 41.9 years were recorded before and after a theater performance of one and a half hour and analyzed using the software program PRAAT. Speech samples consisted of the combination of sustained phonation and continuous speech. For each speech sample the multiparameter index Acoustic Voice Quality Index was calculated. Auditory perceptual evaluations were performed using the GRBASI scale. Questionnaires were used to inventory vocal symptoms and influencing factors. Outcome and results: Acoustic analysis showed a mean AVQI of 3.48 corresponding with a mild dysphonia. Fifty percent of the theater actors reported having (sometimes or regularly) vocal complaints after a performance. The questionnaire revealed a high presence of vocally violent behavior and poor vocal hygiene habits. Objective vocal quality, measured by the AVQI did not change after a theater performance. The auditory perceptual evaluation of the overall grade of dysphonia showed a subtle amelioration of the vocal quality. Conclusion and implications: The results of this study showed the presence of mild dysphonia, regular vocal complaints and poor vocal hygiene habits in theater actors. A theater performance did not have an impact on the objective vocal quality. Further research is necessary to confirm these preliminary results and to investigate the long-term impact of performing on the objective vocal quality.
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Mental distress detection and triage in forum posts: the LT3 CLPsych 2016 shared task system
This paper describes the contribution of LT3 for the CLPsych 2016 Shared Task on automatic triage of mental health forum posts. Our systems use multiclass Support Vector Machines (SVM), cascaded binary SVMs and ensembles with a rich feature set. The best systems obtain macro-averaged F-scores of 40% on the full task and 80% on the green versus alarming distinction. Multiclass SVMs with all features score best in terms of F-score, whereas feature filtering with bi-normal separation and classifier ensembling are found to improve recall of alarming posts.
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Text, history, and philosophy: Abhidharma across scholastic traditions
Tekst, History, and Philosophy. Abhidharma across Buddhist Scholastic Traditions discusses Abhidharmma / Abhidharma as a specific exegetical method. In the first part of the volume, the development of the Buddhist argumentative technique is discussed. The second part investigates the importance of the Buddhist rational tradition for the development of Buddhist philosophy. The third part focuses on some peculiar doctrinal issues that resulted from rational Abhidharmic reflections. In this way, an outline of the development of the Abhidharma genre and of Abhidharmic notions and Concepts in India, Central Asia, China, and Tibet from the life time of the historical Buddha to the tenth century CE is given.
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Floating universal quantifier as a base-generated head in the VP periphery
The universal quantifier niz in Kavalan can immediately precede its DP associate or appear in a quantifier-floating construction where it is separated from its DP associate. This paper argues that floating niz is not derived from its non-floating counterpart as a result of stranding. They differ morphosyntactically and semantically. First of all, while non-floating niz in a negative sentence exhibits scope reconstruction, floating niz in a negative sentence induces scope-freezing effect. Secondly, floating niz should be analyzed as a full-fledged verb, whereas non-floating niz is a nominal modifier. Thirdly, floating niz is not sensitive to A/A' distinction. Fourthly, floating and non-floating niz can co-occur in a sentence. Finally, floating niz can receive interpretations that are not available to non-floating niz. The differences between floating and non-floating niz indicate that they are derivationally distinct. The fact that floating niz is morphosyntactically realized as a verb further suggests that it is base-generated in a functional head in the VP periphery.
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Muscle Tension Dysphagia: Symptomology and Theoretical Framework.
Muscle Tension Dysphagia: Symptomology and Theoretical Framework.
Otolaryngol Head Neck Surg. 2016 Jun 28;
Authors: Kang CH, Hentz JG, Lott DG
Abstract
OBJECTIVE: To identify symptoms, common diagnostic findings, pattern of treatments and referrals offered, and their efficacy in a group of patients with idiopathic functional dysphagia in an otolaryngology setting with multiple providers.
STUDY DESIGN: Case series with chart review.
SETTING: Tertiary academic center.
SUBJECTS AND METHODS: Following Mayo Clinic Institutional Review Board approval, a retrospective chart review was conducted of patients with dysphagia who had a videofluoroscopic swallow study between January 1, 2013, and April 30, 2015. Each patient's dysphagia symptomology, videofluoroscopic swallow study, flexible laryngoscopy, and medical chart were reviewed to identify the treatment paradigms that were utilized.
RESULTS: Sixty-seven adult patients met the inclusion criteria. Abnormal laryngeal muscle tension was present in 97% of patients. Eighty-two percent of patients also demonstrated signs of laryngeal hyperresponsiveness. Nonspecific laryngeal inflammation was evident in 52% of patients. Twenty-seven patients were referred to speech-language pathology for evaluation. Thirteen patients completed a course of voice therapy directed toward unloading muscle tension. All 13 patients self-reported resolution of dysphagia symptoms.
CONCLUSION: The study results suggest that laryngeal muscle tension may be a factor in the underlying etiology in patients with idiopathic functional dysphagia. We propose the diagnostic term muscle tension dysphagia to describe a subset of patients with functional dysphagia. Further prospective studies are needed to better evaluate potential gastroesophageal confounders in this group of patients and to identify an effective paradigm for treatment. In our limited series, speech-language pathology intervention directed toward unloading muscle tension appears effective.
PMID: 27352887 [PubMed - as supplied by publisher]
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SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy
Purpose:
This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a "standard eye." Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to the treatment planning process.
Methods:
Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant.
Results:
The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point.
Conclusion:
The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose
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SU-F-T-134: Can We Use the Same Dose Constrains Learnt From Photon World to Plan Proton for Lung Cancer?
Purpose:
To evaluate if the same DVH constrains used in photon plans can be safely used to plan proton therapy for lung cancer. Since protons and photons have different dose deposition patterns, the hypothesis is following DVH constrains derived from photon world is not safe for proton.
Methods:
We retrospectively evaluated plans for 11 lung cancer patients. Each patient was planned with photon and proton following the same dose constrains. Dose statistics on PTV, normal lung, heart and esophagus were extracted for comparison. gEUD for normal lung was calculated and compared between proton and photon plans. We calculated series of gEUDs for each plan by varying the parameter "a" in gEUD formula from 0.1 to 3, covering the whole confidence interval.
Results:
For all patients, proton plans yield similar PTV coverage and lower dose to heart and esophagus than photon plans. Normal lung V5 was 32.3 % on average in proton plans than 55.4 % in photon. Normal lung gEUD monotonically increased with increasing "a" for all proton and photon plans. For a given patient, the gEUD_proton(a) had a steeper slope than gEUD_photon(a). The two curves crossed for 8 out of 11 patients when "a" = [0.1, 3]. a_crossing ranged from 0.8 to 2.44 with an average of 1.15. For a
Conclusion:
The current clinical guideline is the lower normal lung V5 would associated with less complications. However, proton plans with a lower normal lung V5 could yield a higher gEUD than photon if the real "a" is larger than a_crossing. Since a_crossing was within the possible range of real "a", simply following the normal lung V5 guideline for proton plan would not be a good practice. More comprehensive methods should be developed to evaluate the proton plan.
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SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials
Purpose:
This work investigated the proton tissue-equivalence of various 3D printed materials.
Methods:
Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material.
Results:
The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve.
Conclusion:
While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP.
This work was supported by PHS grant CA180803.
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SU-F-T-90: Patterns of Electron IORT Treatments in the U.S., Europe and Asia
Purpose:
We analyzed data collected from worldwide centers active in electron IORT with a focus on the technical variables of the treatment. Particular attention was given to the dominant tumor sites.
Methods:
54 Mobetron users from 14 countries in clinical operation prior to December 31, 2014, were invited to participate in this study. 29 centers contributed to this survey in sufficient detail to be included in this report. 6,035 patients were treated since 1997. Parameters were analyzed separately for each treatment site. However, special attention was given to the breast cancer, which turned out to be dominant tumor site.
Results:
The average number of patients treated per year in each center was 41 and exceeded 100 patients/year in 3 centers. For data received, 70% of patients worldwide were treated for breast cancer (93% in Europe, 14% in the U.S. and 21% in Asia). In 31% of cases electron IORT was the only breast irradiation. In breast patients, 9 MeV was used in 50% cases; 4MeV, 6MeV and 12MeV in 2%, 25% and 23% of cases respectively. 85% of patients were treated with field sizes between 4 and 6 cm and 35% of them were treated with 1/2 cm sized applicators. Beveled applicators (0°, 15° and 30° tips) were used in 51%, 33% and 16% of cases respectively. In 55% cases bolus was required with 5mm bolus used twice as often as 10mm. Chest-wall protectors were used in 53% of treatment procedures. For Non-breast data, main sites were: colorectal tumors (31%), pancreatic cancers (20%), extremity sarcomas (13%) and retroperitoneal sarcomas (5%).
Conclusion:
A large variety of tumors have been treated with IORT, with breast, colorectal, pancreas and sarcomas being the most frequently treated sites. This survey shows the most common applicators and energies used to treat each tumor site.
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SU-F-T-146: Comparing Monte Carlo Simulations with Commissioning Beam Data for Mevion S250 Proton Therapy System
Purpose:
To evaluate the Monte Carlo simulated beam data with the measured commissioning data for the Mevion S250 proton therapy system.
Method:
The Mevion S250 proton therapy system utilizes a passive double scattering technique with a unique gantry mounted superconducting accelerator and offers effective proton therapy in a compact design concept. The field shaping system (FSS) includes first scattering foil, range modulator wheel (RMW), second scattering foil and post absorber and offers two field sizes and a total of 24 treatment options from proton range of 5 cm to 32 cm. The treatment nozzle was modeled in detail using TOPAS (TOolkit for PArticle Simulation) Monte Carlo code. The timing feathers of the moving modulator wheels were also implemented to generate the Spread Out Bragg Peak (SOBP). The simulation results including pristine Bragg Peak, SOBP and dose profiles were compared with the data measured during beam commissioning.
Results:
The comparison between the measured data and the simulation data show excellent agreement. For pristine proton Bragg Peaks, the simulated proton range (depth of distal 90%) values agreed well with the measured range values within 1 mm accuracy. The differences of the distal falloffs (depth from distal 80% to 20%) were also found to be less than 1 mm between the simulations and measurements. For the SOBP, the widths of modulation (depth of proximal 95% to distal 90%) were also found to agree with the measurement within 1 mm. The flatness of the simulated and measured lateral profiles was found to be 0.6 % and 1.1 %, respectively.
Conclusion:
The agreement between simulations and measurements demonstrate that TOPAS could be used as a viable platform to proton therapy applications. The matched simulation results offer a great tool and open opportunity for variety of applications.
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SU-F-T-59: The Effect of Radiotherapy Dose On Immunoadjuvants
Purpose:
Combining radiotherapy with immunotherapy is a promising approach to enhance treatment outcomes for cancer patients. This in-vitro study investigated which radiotherapy doses could adversely affect the function of anti-CD40 mAb, which is one of the key immunoadjuvants under investigations for priming such combination therapy.
Methods:
Human monocyte derived THP-1 cells were treated with 100ng/mL of PMA in chamber slides to differentiate into macrophage. The THP-1 differentiated macrophages were treated with 2uL/ml of the anti-CD40 mAb and incubated at 37°C and 5% CO2 for 24 hours. Anti-CD40 mAb treated cells were then irradiated at different doses of x-rays: (0, 2, 4, 6, 8, and 12) Gy using the Small Animal Radiotherapy Research Platform (SARRP). After radiation, the cells were left at 4°C for 2 hours followed by immunofluorescence assay. A Nikon inverted live-cell imaging system with fluorescence microscope was used to image the cells mounted on a slide fixed with Dapi. For comparison, an ELISA assay was performed with the antibody added to 3mL of PBS in multiple 10mm dishes. The 10mm dishes were irradiated at different x-ray dose: (0, 2, 4, 6, 8. 10, 12, and 15) Gy using the SARRP.
Results:
The anti-CD40 mAb activating the macrophages starts to lose their viability due to radiation dose between 8Gy to 12Gy as indicated by the immunofluorescence assay. The ELISA assay, also indicated that such high doses could lead to loss of the mAb's viability.
Conclusion:
This work suggests that high doses like those employed during Stereotactic Ablative Radiotherapy may affect the viability of immunoadjuvants such as anti-CD 40. This study avails in-vivo experiments combining radiotherapy with anti-cd40 to get synergistic outcomes, including in the treatment of metastatic disease.
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SU-F-T-64: An Alternative Approach to Determining the Reference Air-Kerma Rate from Extrapolation Chamber Measurements
Purpose:
Since 2008 the Physikalisch-Technische Bundesanstalt (PTB) has been offering the calibration of 125I-brachytherapy sources in terms of the reference air-kerma rate (RAKR). The primary standard is a large air-filled parallel-plate extrapolation chamber. The measurement principle is based on the fact that the air-kerma rate is proportional to the increment of ionization per increment of chamber volume at chamber depths greater than the range of secondary electrons originating from the electrode x0.
Methods:
Two methods for deriving the RAKR from the measured ionization charges are: (1) to determine the RAKR from the slope of the linear fit to the so-called 'extrapolation curve', the measured ionization charges Q vs. plate separations x or (2) to differentiate Q(x) and to derive the RAKR by a linear extrapolation towards zero plate separation. For both methods, correcting the measured data for all known influencing effects before the evaluation method is applied is a precondition. However, the discrepancy of their results is larger than the uncertainty given for the determination of the RAKR with both methods.
Results:
A new approach to derive the RAKR from the measurements is investigated as an alternative. The method was developed from the ground up, based on radiation transport theory. A conversion factor C(x1, x2) is applied to the difference of charges measured at the two plate separations x1 and x2. This factor is composed of quotients of three air-kerma values calculated for different plate separations in the chamber: the air kerma Ka(0) for plate separation zero, and the mean air kermas at the plate separations x1 and x2, respectively. The RAKR determined with method (1) yields 4.877 µGy/h, and with method (2) 4.596 µGy/h. The application of the alternative approach results in 4.810 µGy/h.
Conclusion:
The alternative method shall be established in the future.
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SU-F-T-116: Predicting IQ and the Risk of Hearing Loss Following Proton Versus Photon Radiotherapy for Pediatric Brain Tumor Patients
Purpose:
The increased sparing of normal tissues in intensity modulated proton therapy (IMPT) compared to photon intensity modulated radiotherapy (IMRT) in brain tumor treatments should translate into improved neurocognitive outcomes. Models were used to estimate the intelligence quotient (IQ) and the risk of hearing loss 5 years post radiotherapy and to compare outcomes of proton against photon in pediatric brain tumors.
Methods:
Patients who had received radical IMRT were randomly selected from our retrospective database: 10 cases each of craniopharyngioma, ependymoma and medulloblastoma, and 20 cases of glioma. The existing planning CT and contours were used to generate IMPT plans. The RBE-corrected dose to brain structures and cochleas were calculated for both IMPT and IMRT. A model was applied to estimate IQ using a Markov chain Monte Carlo technique. The reported incidence of hearing loss as a function of cochlear dose was used to estimate the rate of occurrence.
Results:
The average brain dose was less in all IMPT plans compared to IMRT: ranging from a 6.7% reduction (P=0.003) in the case of medulloblastoma to 38% (P=0.007) for craniopharyngioma. This dose reduction translated into a gain in IQ of 1.9 points on average for protons vs photons for the whole cohort at 5 years post-treatment (P=0.011). In terms of specific diseases, the gains in IQ ranged from 0.8 points for medulloblastoma, to 2.7 points for craniopharyngioma. Hearing loss probability was evaluated on a per-ear-basis and was found to be systematically less for proton versus photon: overall 2.9% versus 7.2% (P
Conclusion:
A novel method was developed to predict neurocognitive outcomes in pediatric brain tumor patients on a case-by-case basis. A modest gain in IQ was systematically observed for proton in all patients. Given the uncertainties within the model used and our reinterpretation, these gains may be underestimated.
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SU-F-T-135: A Retrospective Analysis of the Impact of Range Uncertainty in Brain Patients
Purpose:
We retrospectively evaluate the dosimetric impact of a 3.5% range uncertainty on CTV coverage and normal organ toxicity for a cohort of brain patients.
Methods:
Twenty treatment plans involving 20 brain cancer patients treated with Mevions S250 were reviewed. Forty uncertain plans were made by changing the ranges in original plans by ±3.5% while keeping all devices unchanged. Fidelity to the original plans was evaluated with gamma index. Changes in generalized equivalent uniform dose (gEUD) were reported for the following structures: CTV coverage, brainstem, optic chiasm, and optic nerves. Comparisons were made by plotting the relevant endpoints from the uncertain plans as a function of the same endpoints from the original clinical plan.
Results:
Gamma-index analysis resulted in a 50% pass rate of the uncertain plans using a 90% passing rate and 3%/3mm criterion. A 9.5% decrease in the slope of gEUD plot for the CTV was observed for the 3.5% downward range shift. However, the change in slope did not result in a gEUD change greater than 1.1% for the CTV. The slopes of the gEUD plots for normal structures increased by 3.1% 3.9% 2.4% and 0.2% for the chiasm, brainstem, left optic nerve and right optic nerve respectively. The maximum deviation from the gEUD of the clinical plan for normal structures was: 64% in the chiasm, 31% for the brainstem, and 19% for both optic nerves.
Conclusion:
A retrospective review shows moderate radiobiological impact of range uncertainty in passively scattered proton therapy with sporadic catastrophe. The linear regression analysis on the statistical data indicates a systematic deviation of gEUD from treatment planning in the light of range uncertainty.
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SU-F-T-152: Experimental Validation and Calculation Benchmark for a Commercial Monte Carlo Pencil BeamScanning Proton Therapy Treatment Planning System in Heterogeneous Media
Purpose:
Eclipse AcurosPT 13.7, the first commercial Monte Carlo pencil beam scanning (PBS) proton therapy treatment planning system (TPS), was experimentally validated for an IBA dedicated PBS nozzle in the CIRS 002LFC thoracic phantom.
Methods:
A two-stage procedure involving the use of TOPAS 1.3 simulations was performed. First, Geant4-based TOPAS simulations in this phantom were experimentally validated for single and multi-spot profiles at several depths for 100, 115, 150, 180, 210 and 225 MeV proton beams, using the combination of a Lynx scintillation detector and a MatriXXPT ionization chamber array. Second, benchmark calculations were performed with both AcurosPT and TOPAS in a phantom identical to the CIRS 002LFC, with the exception that the CIRS bone/mediastinum/lung tissues were replaced with similar tissues that are predefined in AcurosPT (a limitation of this system which necessitates the two stage procedure).
Results:
Spot sigmas measured in tissue were in agreement within 0.2 mm of TOPAS simulation for all six energies, while AcurosPT was consistently found to have larger spot sigma (calibration by MatriXXPT, the agreements between profiles measurements and TOPAS simulation, and calculation benchmarks are over 97% except near the end of range using 2 mm/2% gamma criteria. Overdosing and underdosing were observed at the low and high density side of tissue interfaces, respectively, and these increased with increasing depth and decreasing energy. Near the mediastinum/lung interface, the magnitude can exceed 5 mm/10%. Furthermore, we observed >5% quenching effect in the conversion of Lynx measurements to dose.
Conclusion:
We recommend the use of an ionization chamber array in combination with the scintillation detector to measure absolute dose and relative PBS spot characteristics. We also recommend the use of an independent Monte Carlo calculation benchmark for the commissioning of a commercial TPS.
Partially supported by Varian Medical System under the master agreement between Varian and University of pennsylvania
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SU-F-T-87: Comparison of Advanced Radiotherapy Techniques for Post- Mastectomy Breast Cancer Patients
Purpose:
To determine if bolus electron conformal therapy (Bolus-ECT) combined with intensity modulated x-ray therapy (IMXT) and flattening filter free volumetric modulated arc therapy (FFF-VMAT (6x and 10x)) can maintain equal or better dose coverage than standard volumetric modulated arc therapy (Std-VMAT) while reducing doses to organs at risk (OARs).
Methods:
Bolus-ECT with IMXT, FFF-VMAT, and Std-VMAT treatment plans were produced for ten post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic. The treatment plans were created on commercially available treatment planning system (TPS) and all completed treatment plans were reviewed and approved by a radiation oncologist. The plans were evaluated based on planning target volume (PTV) coverage, tumor control probability (TCP), dose homogeneity index (DHI), conformity index (CI), and dose to organs at risk (OAR).
Results:
All techniques produced clinically acceptable PMRT plans. Overall, Bolus-ECT with IMXT exhibited higher maximum dose compared to all VMAT techniques. Bolus-ECT with IMXT and FFF-VMAT10x had slightly improved TCP over FFF-VMAT6x and Std-VMAT. However, all VMAT techniques showed improved CI and DHI over Bolus-ECT with IMXT. All techniques showed very similar mean lung dose. Bolus-ECT with IMXT exhibited a reduced mean heart dose over Std-VMAT. Both FFF-VMAT techniques had higher mean heart dose compared to Std-VMAT. In addition, Bolus-ECT with IMXT was able to reduce mean dose to the contralateral breast compared to Std-VMAT and both FFF-VMAT techniques had comparable but slightly reduced dose compared to Std-VMAT.
Conclusion:
This work has shown that Bolus-ECT with IMXT produces clinically acceptable plans while reducing OAR doses. Both FFF-VMAT techniques are comparable to Std-VMAT with slight improvements. Even though all VMAT techniques produce more homogenous and conformal dose distributions, Bolus-ECT with IMXT is a viable option for treating post-mastectomy patients possibly leading to reduced risks of normal tissue complications.
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Massive Upper Airway Bleeding: A Rare Case of Aorto Bronchial Fistula
Clinical presentation of haemoptysis and haematemesis often generates confusion, becoming a difficult task to determine the source of upper airway bleeding. Aortobronchial fistulae is a rare entity, but has been a reported complication in patients that have undergone aortic vascular surgery. A high clinical suspicion is fundamental to making this diagnosis. A 69 year old male, with a previous diagnosis of chronic gastritis, is admitted to the emergency room for vomiting blood. In the first 24 hours after admission, the patient develops respiratory insufficiency after an episode of massive bleeding from his mouth. A computed tomography is performed, which shows a descending thoracic aortic aneurism and signs of aortobronchial fistulae. Urgent thoracic endovascular repair was performed. Early symptoms of aortobronchial fistulae are nonspecific which complicates the diagnosis and can lead to treatment delay. The use of bronchoscopy in these cases is controversial.
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Antioxidant Activity and Characterization of One New Polysaccharide Obtained from Perigord Truffle (Tuber huidongense)
As a medicinal and edible fungus parasitizing on the trees, Perigord Truffle (Tuber huidongense) is well known for its delicious taste, unique smell, and high medical value for healthcare. One new water-soluble nonstarch polysaccharide (PST-W with the yield of 0.41%) from Perigord Truffle (Tuber huidongense) was purified and identified on structural characteristics for the first time. The characterizations of PST-W were studied on physicochemical properties, main components of monosaccharide(s), and molecular structure. The monosaccharide compositions of PST-W were studied and identified as glucan, only containing D-glucoses with the molecular structure of [→6) α-D-Glcp α-D-Glcp (1→]n by methylation analysis and NMR. In the determination of total reducing capacity, the reducing abilities of polysaccharide extracts could be listed as vitamin C > PST-W > crude polysaccharides-3 > crude polysaccharides-2 > crude polysaccharides-1. All of PST-W, crude polysaccharides-2, and crude polysaccharides-3 were relatively good scavenger for 1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radicals with IC50 of 2.81, 4.17, and 3.44 mg/mL, respectively. However, clearing abilities of PST-W and crude polysaccharides were obviously weaker. The activities of total crude extract were the worst, indicating that the impurities might negatively affect the antioxidant activity. Thus, the separation and purification of polysaccharides were significant to increase the antioxidant activity in some degree.
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Essential Oil of Ocimum basilicum L. and (−)-Linalool Blocks the Excitability of Rat Sciatic Nerve
The racemate linalool and its levogyrus enantiomer [(−)-LIN] are present in many essential oils and possess several pharmacological activities, such as antinociceptive and anti-inflammatory. In this work, the effects of essential oil obtained from the cultivation of the Ocimum basilicum L. (EOOb) derived from Germplasm Bank rich in (−)-LIN content in the excitability of peripheral nervous system were studied. We used rat sciatic nerve to investigate the EOOb and (−)-LIN effects on neuron excitability and the extracellular recording technique was used to register the compound action potential (CAP). EOOb and (−)-LIN blocked the CAP in a concentration-dependent way and these effects were reversible after washout. EOOb blocked positive amplitude of 1st and 2nd CAP components with IC50 of and mg/mL, respectively. For (−)-LIN, these values were and mg/mL. Both components reduced the conduction velocity of CAP and the 2nd component seems to be more affected than the 1st component. In conclusion EOOb and (−)-LIN inhibited the excitability of peripheral nervous system in a similar way and potency, revealing that the effects of EOOb on excitability are due to the presence of (−)-LIN in the essential oil.
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Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites
Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer.
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Immediate effect of Mgso4 nebulisation in post operative cardiac patients with COPD
2016-06-30T06-14-35Z
Source: International Journal of Therapies and Rehabilitation Research
Dipmala Nikhil Silajiya, Urjita Pranav Modi, Nimesh Varlekar, Nita Jayprakash Vyas.
COPD patients are prone to develop bronchospasm and risk going to be increased after major surgery like CABG.Mgso4 as an adjunct has a pivotal role in the management of bronchospasm, improving PEFR and stabilising other respiratory parameters along with cardiac stability. This study shows improvement in respiratory parameters and so improve patients outcome and also hospital stay.
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Local Fibrinolysis in Spontaneous Supratentorial Hematomas: Comparison with Surgical and Medical Treatment
Objective: To evaluate the effectiveness of minimally invasive craniopuncture with local fibrinolysis in the management of supratentorial spontaneous intracerebral hemorrhage (SICH). Methods: The study included 218 consecutive patients with supratentorial SICH who were assigned to one of three groups: treated with minimally invasive craniopuncture with local fibrinolysis, treated with craniotomy or other minimally invasive techniques without local fibrinolysis, or receiving conservative management alone. Results: Minimally invasive craniopuncture with local fibrinolysis was associated with a lower rate of assisted ventilation, a shorter period of in-hospital stay, a more frequent initiation of early rehabilitation, and a lower mortality rate at all periods of assessment. The overall mortality at 12 months was 19.4% (vs. 50.0 and 33.3% in the two other therapy groups). Lobar (subcortical and cortical) SICHs treated with local fibrinolysis had an overall mortality of 4.8% (vs. 43.5 and 41.7% in the two other therapy groups). On the other hand, SICHs having mixed (basal ganglia and lobar) locations treated with medical therapy alone had an overall mortality of 28.6%, while associated surgery with or without local fibrinolysis increased the overall mortality to over 65%. Conclusions: The study demonstrated the applicability of minimally invasive craniopuncture with local fibrinolysis for the management of supratentorial SICHs and the advantages it may have in certain categories of patients. The method proved particularly useful in lobar SICHs, being associated with the lowest mortality. Mixed SICHs do not represent a predilection for surgical interventions; however, the results related to mixed supratentorial locations need confirmation in larger cohorts.
Intervent Neurol 2016;5:165-173
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Intervent Neurol 2016;5:165-173
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The spatiotemporal hemodynamic response function for depth-dependent functional imaging of human cortex
Source:NeuroImage, Volume 139
Author(s): Alexander M. Puckett, Kevin M. Aquino, P.A. Robinson, Michael Breakspear, Mark M. Schira
The gray matter of human cortex is characterized by depth-dependent differences in neuronal activity and connections (Shipp, 2007) as well as in the associated vasculature (Duvernoy et al., 1981). The resolution limit of functional magnetic resonance imaging (fMRI) measurements is now below a millimeter, promising the non-invasive measurement of these properties in awake and behaving humans (Muckli et al., 2015; Olman et al., 2012; Ress et al., 2007). To advance this endeavor, we present a detailed spatiotemporal hemodynamic response function (HRF) reconstructed through the use of high-resolution, submillimeter fMRI. We decomposed the HRF into directions tangential and perpendicular to the cortical surface and found that key spatial properties of the HRF change significantly with depth from the cortical surface. Notably, we found that the spatial spread of the HRF increases linearly from 4.8mm at the gray/white matter boundary to 6.6mm near the cortical surface. Using a hemodynamic model, we posit that this effect can be explained by the depth profile of the cortical vasculature, and as such, must be taken into account to properly estimate the underlying neuronal responses at different cortical depths.
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Data-driven forward model inference for EEG brain imaging
Publication date: 1 October 2016
Source:NeuroImage, Volume 139
Author(s): Sofie Therese Hansen, Søren Hauberg, Lars Kai Hansen
Electroencephalography (EEG) is a flexible and accessible tool with excellent temporal resolution but with a spatial resolution hampered by volume conduction. Reconstruction of the cortical sources of measured EEG activity partly alleviates this problem and effectively turns EEG into a brain imaging device. The quality of the source reconstruction depends on the forward model which details head geometry and conductivities of different head compartments. These person-specific factors are complex to determine, requiring detailed knowledge of the subject's anatomy and physiology. In this proof-of-concept study, we show that, even when anatomical knowledge is unavailable, a suitable forward model can be estimated directly from the EEG. We propose a data-driven approach that provides a low-dimensional parametrization of head geometry and compartment conductivities, built using a corpus of forward models. Combined with only a recorded EEG signal, we are able to estimate both the brain sources and a person-specific forward model by optimizing this parametrization. We thus not only solve an inverse problem, but also optimize over its specification. Our work demonstrates that personalized EEG brain imaging is possible, even when the head geometry and conductivities are unknown.
Graphical abstract
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Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm
Among non-small cell lung cancer (NSCLC), adenocarcinoma (AC), and squamous cell carcinoma (SCC) are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR), can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.
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Use of Mercury in Dental Silver Amalgam: An Occupational and Environmental Assessment
The objective of this study was to assess the occupational exposure to mercury in dentistry and associated environmental emission in wastewater of Lahore, Pakistan. A total of ninety-eight blood samples were collected comprising 37 dentists, 31 dental assistants, and 30 controls. Results demonstrate that the dentistry personnel contained significantly higher mean concentration of mercury in their blood samples (dentists: 29.835 µg/L and dental assistants: 22.798 µg/L) compared to that of the controls (3.2769 µg/L). The mean concentration of mercury was found maximum in the blood samples of older age group (62.8 µg/L) in dentists and (44.3 µg/L) in dental assistants. The comparison of mercury concentration among dentists, dental assistants, and controls (pairing based on their ages) revealed that the concentration increased with the age and experience among the dentists and dental assistants. Moreover, the mercury concentration in all the studied dental wastewater samples, collected from twenty-two dental clinics, was found to be exceeding the recommended discharge limit of 0.01 mg/L. Therefore, we recommend that immediate steps must be taken to ensure appropriate preventive measures to avoid mercury vapors in order to prevent potential health hazards to dentistry personnel. Strong regulatory and administrative measures are needed to deal with mercury pollution on emergency basis.
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Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations
Abstract
Introduction
Expert judgement has a role in model-based economic evaluations (EEs) of healthcare interventions. This study aimed to produce reporting criteria for two types of study design to use expert judgement in model-based EE: (i) an expert elicitation (quantitative) study; and (ii) a Delphi study to collate (qualitative) expert opinion.
Methods
A two-round online Delphi process identified the degree of consensus for four core definitions (expert; expert parameter values; expert elicitation study; expert opinion) and two sets of reporting criteria in a purposive sample of experts. The initial set of reporting criteria comprised 17 statements for reporting a study to elicit parameter values and/or distributions and 11 statements for reporting a Delphi survey to obtain expert opinion. Fifty experts were invited to become members of the Delphi process panel by e-mail. Data analysis summarised the extent of agreement (using a pre-defined 75 % 'consensus' threshold) on the definitions and suggested reporting criteria. Free-text comments were analysed using thematic analysis.
Results
The final panel comprised 12 experts. Consensus was achieved for the definitions of expert (88 %); expert parameter values (83 %); and expert elicitation study (83 %). The panel recommended criteria to use when reporting an expert elicitation study (16 criteria) and a Delphi study to collate expert opinion (11 criteria).
Conclusion
This study has produced guidelines for reporting two types of study design to use expert judgement in model-based EE: (i) an expert elicitation study requiring 16 reporting criteria; and (ii) a Delphi study to collate expert opinion requiring 11 reporting criteria.
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IJMS, Vol. 17, Pages 1042: Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques
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IJMS, Vol. 17, Pages 1032: Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma
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IJMS, Vol. 17, Pages 1039: Prognostic Value of Affective Symptoms in First-Admission Psychotic Patients
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Penile Squamous Cell Carcinoma
N/A
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Pyogenic Granuloma in a Patient on Gefitinib
N/A
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Endometrial Tuberculosis Simulating an Ovarian Cancer: a case report
Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical findings are non-specific, its diagnosis can be difficult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computed Tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic Resonance Imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an inflammatory infiltrate with giant cells of type Langhans and bacteriological culture identified Mycobacterium tuberculosis.
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