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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Τετάρτη 29 Ιουνίου 2016
Study of NC-6004 in Combination With 5-FU and Cetuximab in Patients With Head and Neck Cancer
Condition: Head and Neck Neoplasms
Interventions: Drug: NC-6004; Drug: Cetuximab; Drug: 5-FU
Sponsors: Orient Europharma Co., Ltd.; Nanocarrier Co., Ltd.
Recruiting - verified June 2016
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Interventions: Drug: NC-6004; Drug: Cetuximab; Drug: 5-FU
Sponsors: Orient Europharma Co., Ltd.; Nanocarrier Co., Ltd.
Recruiting - verified June 2016
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Iododerma from Contrast Material: NEJM Case Report
- NEJM reports a image case of iododerma, patient after Intravenous urography, Several hours later, generalized pustular eruptions developed, with multiple coalescing vesicles and pus-filled bullae observed on the patient's face and ears, his trunk, and his arms and legs.
- Although its pathogenesis is not understood, delayed iodine clearance and the induction of neutrophil degranulation have been proposed as mechanisms.
- Treatment with thalidomide was initiated, and the skin lesions completely resolved within 4 weeks.
Famous Radiology Blog http://ift.tt/1MM2hKr TeleRad Providers at http://ift.tt/1NgppuI Mail us at sales@teleradproviders.com
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3D Helical and 2D Rhomboidal Supramolecules: Stepwise Self-Assembly and Dynamic Transformation of Terpyridine-Based Metallo-Architectures
Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04482D, Communication
DOI: 10.1039/C6CC04482D, Communication
Die Liu, Zhilong Jiang, Ming Wang, Xiaoyu Yang, Haisheng Liu, Mingzhao Chen, Charles N. Moorefield, George R Newkome, Xiaopeng Li, Pingshan Wang
A Ru2+-connected, metallo-organic ligand (L) with three free terpyridines was designed and synthesized. L was assembled with Zn2+ to generate a helical structure; however, when mixing L with 1,2,3-tristerpyridine ligand...
The content of this RSS Feed (c) The Royal Society of Chemistry
A Ru2+-connected, metallo-organic ligand (L) with three free terpyridines was designed and synthesized. L was assembled with Zn2+ to generate a helical structure; however, when mixing L with 1,2,3-tristerpyridine ligand...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Gold-Catalyzed Intermolecular Formal (3+2) Cycloaddition of Stabilized Vinyldiazo Derivatives and Electronically Unbiased Allenes
Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04106J, Communication
DOI: 10.1039/C6CC04106J, Communication
Enol Lopez, Giacomo Lonzi, Francisco Javier Gonzalez , Luis A. Lopez
The reaction of electronically unbiased allenes with alkenyldiazo compounds in the presence of gold catalysts provided alkylidenecyclopentene derivatives resulting from a formal intermolecular (3+2) carbocyclization. A stepwise mechanism involving initial...
The content of this RSS Feed (c) The Royal Society of Chemistry
The reaction of electronically unbiased allenes with alkenyldiazo compounds in the presence of gold catalysts provided alkylidenecyclopentene derivatives resulting from a formal intermolecular (3+2) carbocyclization. A stepwise mechanism involving initial...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Cavity-Containing Supramolecular Gels as a Crystallization Tool for Hydrophobic Pharmaceuticals
Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04037C, Communication
DOI: 10.1039/C6CC04037C, Communication
Lena Kaufmann, Stuart R. Kennedy, Christopher David Jones, Jonathan W Steed
We present two approaches to low-molecular-weight supramolecular gels bearing hydrophobic cavities based on calixarene-containing building blocks. Gels are formed by a calixarene based tetrahydrazide gelator or a co-gel of a...
The content of this RSS Feed (c) The Royal Society of Chemistry
We present two approaches to low-molecular-weight supramolecular gels bearing hydrophobic cavities based on calixarene-containing building blocks. Gels are formed by a calixarene based tetrahydrazide gelator or a co-gel of a...
The content of this RSS Feed (c) The Royal Society of Chemistry
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Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases
Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.
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10 obsolete EMT skills
Nothing makes me feel older than when I drop a casual reference to an EMT skill in a continuing education class and several bewildered young EMTs raise their hands hesitantly and ask, "Kelly, what are MAST pants""
It got me to thinking how different the EMS profession is now from what it was when my career began. Medicine is a continually evolving process, and advances in technology come so rapidly that the current generation of EMS providers is working with a markedly different knowledge base and set of skills than the last one.
So gather around the campfire children and let Uncle Kelly tell you how we did it in the old days. Each of these 10 skills is something we used to commonly do, but are rarely, if ever, used any longer.
10. Pneumatic Anti-Shock Garments
I only spell it out because if I said MAST or PASG, I'd still have to explain it to you young whippersnappers. See, back in the day we used to put these inflatable Velcro pants on shock patients, and when inflated, it raised their blood pressure. It did raise blood pressure very well — to the point that the patient bled pink from all the IV fluids we gave, but those magic pants sucked at saving lives.
Not only did we have to know the different methods of applying them, like the diaper method and the pajama method, we also had to memorize the criteria for removal. Dinosaurs, say them with me now: "Bilateral large bore IV access, two units of typed and matched blood, surgical team on standby, deflate the abdominal section for 10 seconds, recheck the blood pressure …"
9. Manual defibrillation paddles
You kids these days with your hippity-hop music and your iThings and your hands-free multifunction electrodes.… Why, in my day, when we wanted to defibrillate someone, we had these things called paddles. And you had to apply conductive gel to them and smear it around; then you had to press them on the chest with at least 25 pounds of paddle pressure
And you had your energy select dial and defib button right there on the paddles. And you did this thing called a quick look, so that you could immediately shock the patient, like, three times in a row, before you even attached the monitor leads.
And by God, we were grateful.
8. Esophageal Obturator Airways
Imagine if a Combitube and a BVM had a baby, and the airway baby inherited the worst features of each. The EOA was a supraglottic airway that was bulky, often caused trauma on insertion, did a poor job of isolating the trachea and protecting against aspiration and still required that you maintain a mask seal.
And to think that nobody uses these beauties anymore! Crazy, right"
7. Oral screws
Picture — because I am afraid of what you might stumble across if you Google "oral screws" — if you will a little plastic doohickey shaped like a miniature ice cream cone with threads on the outer surface and a T-handle on the large end. And what you did was insert the small end of this doohickey between someone's teeth when their jaws were clenched, and screwed it in until it forced their jaws apart.
We used to do this whenever someone had a seizure, in the mistaken belief that if we didn't get their mouth open, they'd swallow their tongue.
But the real reason was that it gave paramedics with a juvenile sense of humor the opportunity to hold out their hands and bark, "Gimme an oral screw!"
I'm telling you, that one never got old.
6. Taping stuff down
When I was a paramedic student, my instructor took great pains to show us how to tear thin little strips of adhesive tape to secure IV catheters and endotracheal tubes. We fashioned elegant little chevrons of tape over the wings on our IV catheter hubs (seriously, they had wings) to secure them without obscuring the cannulation site. And we used to tear a one-inch strip of tape longitudinally for a few inches, wrapping one strip around the endotracheal tube and the other across the face like a big mustache.
And then someone would promptly rip our IV or endotracheal tube out while we were loading the patient, so we got to do it again.
Nowadays we have tube holders and IV dressings, and taping is a lost art like calligraphy and darning your socks.
5. Rotating tourniquets
Once upon a time, we used to think that acute pulmonary edema and decompensated congestive heart failure was caused by too much blood re-entering the lungs. We thought that if we could trap blood in the extremities, we'd reduce preload enough to relieve the pulmonary edema.
So we applied humongous blood pressure cuffs on three of the patient's four extremities, inflated them to just above diastolic pressure, and rotated them around the patient's extremities every 15 minutes.
And it took us only a generation or so to discover that it was stupid and didn't work.
4. Trendelenburg position
For many years we fervently believed the Trendelenburg position was a vital treatment for shock. We thought that elevating the feet higher than the head raised blood pressure, and maybe even caused a couple units of blood to flow from the legs to the trunk.
Turns out it doesn't really do those things, and instead caused respiratory decompensation and a rise in intracranial pressure. Still, that doesn't keep some EMTs working for the EMS Agency That Time Forgot from carefully applying and documenting "patient placed in Trendelenburg position."
3. Standing takedowns
Now that our current understanding of spinal cord injury acknowledges that prehospital spinal immobilization on backboards has virtually no supporting evidence and probably does more harm than good, we're boarding far fewer people these days.
While the adage holds true that "absence of evidence does not mean evidence of absence," and there may be some yet-undiscovered tiny subset of patients that benefit from strapping a curved body to a flat board, it's a pretty safe bet that subset does not include people walking around the scene under their own power.
2. External jugular IV access
Honestly, I really miss this one. The EJ used to be my go-to vein in a code. I was already right there at the head intubating, and all it took was turning the patient's head to one side a bit, sinking a 14-gauge in that fat, engorged vein, and you had the mother of all peripheral IV accesses.
You know, we did this so all those questionably beneficial drugs we gave could reach the heart that much faster. Now, with mechanical IO devices like the EZ-IO in my repertoire, I can't remember the last time I started an EJ.
Adult IO devices have really revolutionized emergency peripheral vascular access. And not a moment too soon, either, before this intracavernous technique really caught on.
1. Radio 10 codes
Once upon a time, we used to take sadistic pleasure in rapid fire broadcasting to the brand-new dispatcher, "Dispatch, we're 10-98, 10-8, 10-19, 10-18 to our 10-42, where we'll be 10-7 for a few minutes for a 10-33 10-100. If we're not 10-2 on that, we'll be happy to 10-9."
Now that we communicate in plain English because 10 codes are confusing and vary between agencies, we get to say, "Dispatch, we've completed our last assignment and are available for call, but we're heading to our station as soon as possible because my partner will be out of service taking an emergency all-he-could-eat taco buffet poop. If you didn't copy all that, I'm willing to repeat it."
Or at least we get to say that once.
I could think of a few more EMT skills that may soon become obsolete if we don't get better at applying them, but that's my list of top 10 obsolete EMT skills.
Got any to add to the list" Chime in with yours in the comments.
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Highly solvatochromic and tunable fluorophores based on a 4,5-quinolimide scaffold: Novel CDK5 probes
Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC04566A, Communication
DOI: 10.1039/C6CC04566A, Communication
Juan A. Gonzalez-Vera, Francisco Fueyo-Gonzalez, Ibon Alkorta, Marion Peyressatre, May C. Morris, ROSARIO HERRANZ
Novel 4,5-quinolimide-based fluorophores are more solvatochromic and red-shifted than known naphthalimide analogues. Conjugation of one of these fluorophores to a peptide derived from CDK5 kinase demonstrated its sensitivity for monitoring...
The content of this RSS Feed (c) The Royal Society of Chemistry
Novel 4,5-quinolimide-based fluorophores are more solvatochromic and red-shifted than known naphthalimide analogues. Conjugation of one of these fluorophores to a peptide derived from CDK5 kinase demonstrated its sensitivity for monitoring...
The content of this RSS Feed (c) The Royal Society of Chemistry
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High oxygen tension increases global methylation in bovine 4-cell embryos and blastocysts but does not affect general retrotransposon expression
Retrotransposons are transposable elements that insert extra copies of themselves throughout the genome via an RNA intermediate using a copy and paste' mechanism. They account for more than 44% of the bovine genome and have been reported to be functional, especially during preimplantation embryo development. In the present study, we tested whether high oxygen tension (20% O-2) influences global DNA methylation analysed by immunofluorescence staining of developing bovine embryos and whether this has an effect on the expression of some selected retrotransposon families. High oxygen tension significantly increased global DNA methylation in 4-cell embryos and blastocysts. A significant expression difference was observed for ERV1-1-I_BT in female blastocysts, but no significant changes were observed for the other retrotransposon families tested. Therefore, the study indicates that global DNA methylation is not necessarily correlated with retrotransposon expression in bovine preimplantation embryos.
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Seroprevalence and risk factors associated with brucellosis as a professional hazard in Pakistan
The present study was conducted to determine the seroprevalence and identify risk factors associated with brucellosis in humans at high risk in the Potohar plateau of northeastern Pakistan. A total of 262 serum samples were collected from persons of different occupational groups: veterinary personnel, milkers, abattoir workers, livestock farmers, and others (drivers, security guards, housewives). Data related to gender, age, occupation, contact with animals, brucellosis-related symptoms, consumption of raw milk, and geographical region were collected. The Rose Bengal plate test and the serum agglutination test were performed to determine the seroprevalence of brucellosis. The overall seroprevalence was found to be 6.9% (95% confidence interval [CI]: 4.1, 10.6). Real-time polymerase chain reaction assay showed that all cases were affected by Brucella abortus. Individuals who consumed raw milk had higher odds of brucellosis seropositivity. This is the first report of human brucellosis related to B. abortus in high-risk professionals from Pakistan by the combined use of serological and molecular methods.
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Seroprevalence and risk factors for brucellosis in a high-risk group of individuals in Bangladesh
Brucellosis is an occupational hazard of livestock farmers, dairy workers, veterinarians, slaughterhouse workers, and laboratory personnel, all of whom are considered to belong to the high-risk occupational group (HROG). A study was undertaken to determine the seroprevalence of brucellosis, identify risk factors associated with brucellosis seropositivity, and detect Brucella at genus level using real-time polymerase chain reaction (PCR) among people in the HROG in the Dhaka division of Bangladesh. A sample of 500 individuals from the HROG was collected from three districts of Dhaka division of Bangladesh. A multiple random effects logistic regression model was used to identify potential risk factors. Two types of real-time PCR methods were applied to detect Brucella genus-specific DNA using serum from seropositive patients. The prevalence of brucellosis based on the three tests was observed to be 4.4% based on a parallel interpretation. The results of the multiple random effects logistic regression analysis with random intercept for district revealed that the odds of brucellosis seropositivity among individuals who had been in contact with livestock for more than 26 years was about 14 times higher as compared to those who had less than 5 years of contact with livestock. In addition, when the contact was with goats, the odds of brucellosis seropositivity were about 60 times higher as compared to when contact was with cattle only. Noticeable variation in brucellosis seropositivity among humans within the three districts was noted. All of the 13 individuals who tested positive for the serological tests were also positive in two types of real-time PCR using the same serum samples. Livestock farmers of brucellosis positive herds had a significantly higher probability to be seropositive for brucellosis. The study emphasized that contact with livestock, especially goats, is a significant risk factor for the transmission of brucellosis among individuals in the HROG.
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Effect of feeding live yeast products to calves with failure of passive transfer on performance and patterns of antibiotic resistance in fecal Escherichia coli
Fifty-two newborn Holstein calves with serum IgG concentrations less than 0.73 g.dL(-1) were randomly assigned to one of four treatments: no added live yeast (control), 0.5 g of live yeast added to the grain for 84 d (SC; Saccharomyces cerevisiae), 0.5 g of live yeast added to the milk for 42 d (SB; S. cerevisiae, spp. boulardii), and 0.5 g of live yeast added to the grain for 84 d and to the milk for 42 d (SCSB). Calves were offered 440 g of milk replacer DM for the first 42 d and grain for ad libitum intake throughout the study. Plasma was analyzed weekly for concentrations of glucose and beta-hydroxybutyrate. Escherichia coli isolated from fecal samples collected every 2 weeks were used for determination of antibiotic resistance patterns. Calves receiving SC consumed more grain DM, had increased weight gain prior to weaning, and increased plasma glucose concentrations compared to controls. Days with diarrhea were reduced by feeding live yeast to calves. Antibiotic resistance in fecal E. coli was associated with the age of calves with highest levels of resistance observed in the 3 d calves. While calves receiving SCSB had higher levels of antibiotic resistance than controls, this effect was not associated with any of the other treatments. Improvements in performance of calves with failure of passive transfer were observed when live yeast was added only to the grain.
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Polish circular migration and marginality: a livelihood strategy approach
White, A; (2016) Polish circular migration and marginality: a livelihood strategy approach. Studia Migracyjne – Przegląd Polonijny , 1 (159) pp. 153-166. Gold open access
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ICME international survey on teachers working and learning through collaboration
Robutti, O; Cusi, A; Clark-Wilson, A; Chapman, O; Esteley, C; Goos, M; Isoda, M; Robutti, O; Cusi, A; Clark-Wilson, A; Chapman, O; Esteley, C; Goos, M; Isoda, M; Jaworski, B; Joubert, M; - view fewer (2016) ICME international survey on teachers working and learning through collaboration. ZDM (In press).
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Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach
McCrory, EJ; Mayes, L; (2015) Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach. Current Addiction Reports , 2 (4) pp. 326-330. 10.1007/s40429-015-0079-2 . Green open access
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Exchange calculations between donors in silicon and metal-phthalocyanine dimer.
Wu, W.; (2007) Exchange calculations between donors in silicon and metal-phthalocyanine dimer. Doctoral thesis, University of London. Green open access
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Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years
Aguiar, R; Araújo, C; Martins-Coelho, G; Isenberg, D; (2016) Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years. Arthritis Care & Research 10.1002/acr.22921 . (In press).
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Elucidating molecular mechanisms of leukaemogenesis in normal karyotype AML.
Smith, S.L-L.; (2008) Elucidating molecular mechanisms of leukaemogenesis in normal karyotype AML. Doctoral thesis, University of London. Green open access
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Optimal Exercise Strategies for Operational Risk Insurance via Multiple Stopping Times
Targino, RS; Peters, GW; Sofronov, G; Shevchenko, PV; (2016) Optimal Exercise Strategies for Operational Risk Insurance via Multiple Stopping Times. Methodology and Computing in Applied Probability 10.1007/s11009-016-9493-8 . (In press). Green open access
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A study of the influence of ethnicity on serology and clinical features in lupus
Morais, SA; Isenberg, DA; (2016) A study of the influence of ethnicity on serology and clinical features in lupus. Lupus 10.1177/0961203316645204 . (In press).
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Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review
Custódio Alves, S; Fasano, S; Isenberg, DA; (2016) Autoimmune gastrointestinal complications in patients with Systemic Lupus Erythematosus: case series and literature review. Lupus 10.1177/0961203316655210 . (In press). Green open access
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Analysis of complete remission in systemic lupus erythematosus patients over a 32-year period
Medina-Quiñones, CV; Ramos-Merino, L; Ruiz-Sada, P; Isenberg, DA; (2016) Analysis of complete remission in systemic lupus erythematosus patients over a 32-year period. Arthritis Care and Research , 68 (7) pp. 981-987. 10.1002/acr.22774 .
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Experiences and perspectives of children attending a weight loss camp in China: a qualitative study
Li, X; Zhou, X; Hesketh, T; (2016) Experiences and perspectives of children attending a weight loss camp in China: a qualitative study. Child: Care, Health and Development 10.1111/cch.12353 . (In press).
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Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo
Hebden, JC; Chitnis, D; Airantzis, D; Highton, D; Williams, R; Phan, P; Giagka, V; Hebden, JC; Chitnis, D; Airantzis, D; Highton, D; Williams, R; Phan, P; Giagka, V; Powell, S; Cooper, RJ; Tachtsidis, I; Smith, M; Elwell, C; Everdell, N; - view fewer (2016) Towards a wearable near infrared spectroscopic probe for monitoring concentrations of multiple chromophores in biological tissue in vivo. Review of Scientific Instruments , 87 (6) , Article 065112. 10.1063/1.4954722 .
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Induced pluripotent stem cell models of frontotemporal dementia
Preza, E; Hardy, J; Warner, T; Wray, S; (2016) Induced pluripotent stem cell models of frontotemporal dementia. Neuropathology and Applied Neurobiology 10.1111/nan.12334 . (In press).
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Observing mealworms in the primary classroom
Tunnicliffe, SD; (2016) Observing mealworms in the primary classroom. Journal of Emergent Science (In press).
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Children's science learning: a core skills approach
Tolmie, AK; Ghazali, Z; Morris, S; (2016) Children's science learning: a core skills approach. British Journal of Educational Psychology 10.1111/bjep.12119 . (In press).
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Evaluation of Transbronchial Lung Cryobiopsy Size and Freezing Time: A Prognostic Animal Study
Background: Transbronchial lung biopsy using a cryoprobe is a novel way of sampling lung parenchyma. Correlation of freezing time with biopsy size and complications has not been evaluated in vivo. Objectives: The primary aim of the study is to evaluate the correlation between transbronchial cryobiopsy freezing time and size. The secondary aims are to evaluate histological quality of the biopsy and evaluate procedure-associated complications. Methods: Transbronchial lung cryobiopsies were obtained from two anaesthetised sheep using a 1.9-mm cryoprobe inserted into a flexible bronchoscope under fluoroscopic guidance. Freezing times ranged from 1 to 6 s (n = 49). The cryobiopsies were evaluated histologically with respect to their size and quality. Complications of bleeding and pneumothorax were recorded. Results: The mean cross-sectional area of the cryobiopsy ranged from 4.7 ± 2.1 to 15.7 ± 15.3 mm2. There was a significant positive correlation between increasing freezing time and cryobiopsy cross-sectional area (p = 0.028). All biopsies contained lung tissue with preserved parenchyma. Crush and freeze artefacts were not observed and tissue architecture was intact in all specimens. Small blood vessels and terminal bronchioles were observed in 88% of specimens. All cryobiopsies caused nil or mild haemorrhage with the exception of only 1 episode of severe haemorrhage at 6 s freezing time. Pneumothoraces occurred at 2, 5 and 6 s freezing time and required chest tube insertion. The most significant haemorrhage and pneumothoraces occurred at 5 and 6 s. Our results suggest an initial freezing time of 3 s can provide the maximal biopsy size while minimising major complications. Conclusion: The optimal transbronchial cryobiopsy freezing time is initially 3 s. This time is associated with minimal complications and large artefact-free biopsies.
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The Feasibility of Tracheal Oxygen Supplementation during Flexible Bronchoscopy
Background: Hypoxemia is a frequent adverse event occurring during flexible bronchoscopy and is usually prevented by close monitoring and, if needed, oxygen supplementation by nasal cannula. Objective: We aim to demonstrate that tracheal oxygen supplementation during flexible bronchoscopy is a feasible, safe and effective method to restore oxygen saturation levels after oxygen desaturation. Methods: In a first phase, we compare oxygen supplementation by the tracheal or nasal route in a single blinded cross-over design in healthy volunteers. In a second phase, we study patients referred for diagnostic flexible bronchoscopy, who desaturate despite oxygen supplementation by nasal cannula, in order to assess the ability to correct hypoxemia through tracheal oxygen supplementation. Results: In the first phase, the mean capillary partial pressure of oxygen was 181 mm Hg when oxygen at a flow rate of 4 liters/min was administered by the tracheal route, compared to 125 mm Hg by the nasal route (p Conclusions: Tracheal oxygen supplementation is safe, feasible and an effective way to restore oxygen saturation levels during flexible bronchoscopy.
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