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Δευτέρα 18 Σεπτεμβρίου 2017

Phase I/II Study of Hypofractionated Intensity-Modulated Radiotherapy for Prostate Cancer including Simultaneously Integrated Boost

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Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Michael G. Chang, Nitai Mukhopadhyay, Diane Holdford, Vicki Skinner, Siddharth Saraiya, Drew Moghanaki, Mitchell S. Anscher
PurposeTo evaluate the safety and efficacy of moderately hypofractionated radiotherapy with simultaneous integrated boost (HSIB) IMRT that includes coverage of the seminal vesicles (SV) and pelvic lymph nodes (LN).MethodsMen with localized prostate cancer were prospectively enrolled in a phase I/II trial to receive HSIB-IMRT to the prostate, ±SV, ±pelvic LN using a risk-based method. Low-risk (LR) patients received 69.6Gy to only the prostate in 29 fractions. Intermediate- (IR) and high-risk (HR) patients received 30 fractions with 72Gy to the prostate, 54Gy to the SV, and 50.4Gy to the pelvic LN when risk of LN involvement exceeded 15% by the Roach formula. IR and HR patients received androgen deprivation therapy. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated with patient and physician reported surveys.ResultsFifty-five men were enrolled and 49 had at least one year of follow up with 19.2% LR, 40.4% IR, and 40.4% HR disease. The median age was 69years and median follow-up time was 36.9months. Twenty-six patients received pelvic nodal HSIB-IMRT. At 2years, the cumulative incidence of physician-reported late grade 2+ GU and GI toxicity were 32.6%, and 18.4% respectively. At 2-years, only 10.2% grade 2+ GU toxicities and 2.0% grade 2+ GI toxicities remained unresolved. At last follow up, the prevalence of unresolved physician-reported late grade 2+ GU and GI toxicity was 4.1% and 0%. The median patient-reported AUA-IPSS score fell from 10 at baseline to 7.5 at 2years. The 3-year biochemical relapse-free survival rate for the cohort was 96%.ConclusionsHSIB-IMRT with risk-based nodal coverage results in excellent biochemical control. While the cumulative incidence of physician-reported GU toxicity was higher than anticipated, late GI and GU toxicity was relatively transient.



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Pilot Study on the Impact of F18-Labeled Thymidine PET/CT on Gross Tumor Volume Identification and Definition for Pancreatic Cancer

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Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Jennifer L. Pretz, Michael A. Blake, Joseph H. Killoran, Harvey J. Mamon, Jennifer Y. Wo, Andrew X. Zhu, Theodore S. Hong
PurposeAccurate target definition for radiotherapy planning in localized pancreatic cancer is critical, particularly when using strategies that omit elective coverage. Standard imaging modalities such as CT, MRI, and endoscopic ultrasound have limited concordance with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)-PET can also be difficult to interpret, as increased activity is indicative of increased glucose metabolism, rather than cellular proliferation. F18 – labeled thymidine (FLT) is a proliferative marker which exploits the expression of pyrimidine-metabolizing enzymes. We evaluate the impact of FLT-PET on pancreatic target definition for radiation planning.Methods and MaterialsPatients with biopsy proven, newly diagnosed, untreated pancreatic adenocarcinoma were enrolled on an IRB-approved prospective study. Patients were injected with FLT and scanned 20–30minutes later. Two physicians (referred to as observer 1 and observer 2) independently contoured the gross tumor volume (GTV) and involved nodes on CT scan only, and then again with the assistance of co-registered FLT-PET. Conformality index (CI), the ratio of the volumes of intersection and union, was used as the metric for volume comparison (where CI=0 represented no overlap and CI=1 represented perfect overlap).ResultsNine patients were enrolled on this study. FLT-avidity was discerned in 8 of 9 patients. Average CT-GTV volume for observers 1 and 2 was 38.1cc and 26.5cc respectively. Average FLT-GTV volume for observers 1 and 2 was 39.1cc and 25.0cc respectively. For the 8 patients with FLT-avid tumors, addition of FLT data improved concordance of GTV definition between physicians in 6 of 8 tumors. Average CI for inter-observer CT-GTV was 0.325. Addition of FLT-PET information improved average CI to 0.400.ConclusionFLT-PET improves inter-observer concordance in GTV definition. Further studies will focus on verification of these findings, pathologic verification of the FLT-PET signal, and optimization of the FLT-PET signal threshold for auto-segmentation.



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Proton Craniospinal Irradiation During the Third Trimester of Pregnancy

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Publication date: Available online 18 September 2017
Source:Practical Radiation Oncology
Author(s): Anusha Kalbasi, Maura Kirk, Boon-Keng Kevin Teo, Eric Diffenderfer, Xuanfeng Ding, James McDonough, Erin Murphy, Christine Hill-Kayser




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Mitochondrial Nanotunnels

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Publication date: Available online 19 September 2017
Source:Trends in Cell Biology
Author(s): Amy E. Vincent, Doug M. Turnbull, Veronica Eisner, György Hajnóczky, Martin Picard
Insight into the regulation of complex physiological systems emerges from understanding how biological units communicate with each other. Recent findings show that mitochondria communicate at a distance with each other via nanotunnels, thin double-membrane protrusions that connect the matrices of non-adjacent mitochondria. Emerging evidence suggest that mitochondrial nanotunnels are generated by immobilized mitochondria and transport proteins. This review integrates data from the evolutionarily conserved structure and function of intercellular projections in bacteria with recent developments in mitochondrial imaging that permit nanotunnel visualization in eukaryotes. Cell type-specificity, timescales, and the selective size-based diffusion of biomolecules along nanotunnels are also discussed. The joining of individual mitochondria into dynamic networks of communicating organelles via nanotunnels and other mechanisms has major implications for organelle and cellular behaviors.



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Influence of obesity on experimental periodontitis in rats: histopathological, histometric and immunohistochemical study

Abstract

Objectives

This study assessed the influence of obesity on the progression of ligature-induced periodontitis in rats.

Materials and methods

Forty-eight adult Wistar rats were randomly divided into two groups: the HL group (n = 24) was fed high-fat animal food to induce obesity, and the NL group (n = 24) was fed normolipidic animal food. Obesity was induced within a period of 120 days, and the induction of experimental periodontitis (EP) was subsequently performed for 30 days. The animals were euthanized after 7, 15, and 30 days, and the jaws were removed for histopathological, histometric, and immunohistochemical analyses. Tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear factor kappa beta ligand (RANKL), and osteoprotegerin (OPG) were analyzed via immunolabeling.

Results

Histological findings indicated that the inflammation was more extensive and lasted longer in the HL⁄EP; however, advanced destruction also occurred in the NL/EP. Greater bone loss was verified in the HL/EP group (2.28 ± 0.35) in the period of 7 days than in the NL/EP group (1.2 ± 0.29). High immunolabeling was identified in the HL/EP group in the initial periods for RANKL and TRAP, whereas the NL⁄EP group presented with moderate immunolabeling for both factors. The HL/EP and NL/EP groups showed low immunolabeling for OPG.

Conclusions

Obesity induced by a high-fat diet influenced alveolar bone metabolism when associated with experimental periodontitis and caused a more severe local inflammatory response and alveolar bone loss.

Clinical relevance

Obesity is related to greater alveolar bone loss and an accentuated local inflammatory response, which may be reflected in the clinical severity of periodontitis and dental loss.



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Peripheral T-cell lymphomas:focusing on novel agents in relapsed and refractory disease

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Publication date: Available online 17 September 2017
Source:Cancer Treatment Reviews
Author(s): Alessandro Broccoli, Lisa Argnani, Pier Luigi Zinzani
Patients with relapsed or refractory peripheral T-cell lymphoma display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory PTCL. Four recently approved compounds are used as single agents: pralatrexate, a novel antifolate agent; romidepsin and belinostat, both histone deacetylase (HDAC) inhibitors; brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody. Several other molecules have demonstrated their activity in the same context: gemcitabine, bendamustine, lenalidomide, duvelisib, copanlisib, alisertib, mogamulizumab, selinexor and ARGX-110. Robust preclinical observations strongly support chemo-free combinations, which are expected to enhance the quality and duration of responses in pretreated patients and in those who are unable to receive a stem cell transplantation.



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The relationship between CO 2 emission, energy consumption and economic growth in Malaysia: a three-way linkage approach

Abstract

This study examines the three-way linkage relationships between CO2 emission, energy consumption and economic growth in Malaysia, covering the 1975–2015 period. An autoregressive distributed lag approach was employed to achieve the objective of the study and gauged by dynamic ordinary least squares. Additionally, vector error correction model, variance decompositions and impulse response functions were employed to further examine the relationship between the interest variables. The findings show that economic growth is neither influenced by energy consumption nor by CO2 emission. Energy consumption is revealed to be an increasing function of CO2 emission. Whereas, CO2 emission positively and significantly depends on energy consumption and economic growth. This implies that CO2 emission increases with an increase in both energy consumption and economic growth. Conclusively, the main drivers of CO2 emission in Malaysia are proven to be energy consumption and economic growth. Therefore, renewable energy sources ought to be considered by policy makers to curb emission from the current non-renewable sources. Wind and biomass can be explored as they are viable sources. Energy efficiency and savings should equally be emphasised and encouraged by policy makers. Lastly, growth-related policies that target emission reduction are also recommended.



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Complex organic pollutant mixtures originating from industrial and municipal emissions in surface waters of the megacity Jakarta—an example of a water pollution problem in emerging economies

Abstract

During the last decades, the global industrial production partly shifted from industrialized nations to emerging and developing countries. In these upcoming economies, the newly developed industrial centers are generally located in densely populated areas, resulting in the discharge of often only partially treated industrial and municipal wastewaters into the surface waters. There is a huge gap of knowledge about the composition of the complex organic pollutant mixtures occurring in such heavily impacted areas. Therefore, we applied a non-target screening to comprehensively assess river pollution in a large industrial area located in the megacity Jakarta. More than 100 structurally diverse organic contaminants were identified, some of which were reported here for the first time as environmental contaminants. The concentrations of paper manufacturing chemicals in river water—for example, of the endocrine-disrupting compound bisphenol A (50–8000 ng L−1)—were as high as in pure untreated paper industry wastewaters. The non-target screening approach is the adequate tool for the identification of water contaminants in the new global centers of industrial manufacturing—as the first crucial step towards the evaluation of as yet unrecognized environmental risks.



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Analysis of influence mechanism of energy-related carbon emissions in Guangdong: evidence from regional China based on the input-output and structural decomposition analysis

Abstract

It is important to analyze the influence mechanism of energy-related carbon emissions from a regional perspective to effectively achieve reductions in energy consumption and carbon emissions in China. Based on the "energy-economy-carbon emissions" hybrid input-output analysis framework, this study conducted structural decomposition analysis (SDA) on carbon emissions influencing factors in Guangdong Province. Systems-based examination of direct and indirect drivers for regional emission is presented. (1) Direct effects analysis of influencing factors indicated that the main driving factors of increasing carbon emissions were economic and population growth. Carbon emission intensity was the main contributing factor restraining carbon emissions growth. (2) Indirect effects analysis of influencing factors showed that international and interprovincial trades significantly affected the total carbon emissions. (3) Analysis of the effects of different final demands on the carbon emissions of industrial sector indicated that the increase in carbon emission arising from international and interprovincial trades is mainly concentrated in energy- and carbon-intensive industries. (4) Guangdong had to compromise a certain amount of carbon emissions during the development of its export-oriented economy because of industry transfer arising from the economic globalization, thereby pointing to the existence of the "carbon leakage" problem. At the same time, interprovincial export and import resulted in Guangdong transferring a part of its carbon emissions to other provinces, thereby leading to the occurrence of "carbon transfer."



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Burnout is associated with changes in error and feedback processing

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Publication date: Available online 18 September 2017
Source:Biological Psychology
Author(s): Patrick D. Gajewski, Sylvia Boden, Gabriele Freude, Guy G. Potter, Michael Falkenstein
Burnout is a pattern of complaints in individuals with emotionally demanding jobs that is often seen as a precursor of depression. One often reported symptom of burnout is cognitive decline. To analyze cognitive control and to differentiate between subclinical burnout and mild-to-moderate depression a double-blinded study was conducted that investigates changes in the processing of performance errors and feedback in a task switching paradigm. Fifty-one of 76 employees from emotionally demanding jobs showed a sufficient number of errors to be included in the analysis. The sample was subdivided into groups with low (EE-) and high (EE+) emotional exhaustion and no (DE-) and mild-to-moderate depression (DE+). The behavioral data did not significantly differ between the groups. In contrast, in the EE+ group, the error negativity (Ne/ERN) was enhanced while the error positivity (Pe) did not differ between the groups. After negative feedback the feedback-related negativity (FRN) was enhanced, while the subsequent positivity (FRP) was reduced in EE+ relative to EE-. None of these effects were observed in the DE+ vs. DE-. These results suggest an upregulation of error and negative feedback processing, while the later processing of negative feedback was attenuated in employees with subclinical burnout but not in mild-to-moderate depression.



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Frontoparietal theta oscillations during proactive control are associated with goal-updating and reduced behavioral variability

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Publication date: Available online 18 September 2017
Source:Biological Psychology
Author(s): Patrick S. Cooper, Aaron S.W. Wong, Montana McKewen, Patricia T. Michie, Frini Karayanidis
Low frequency oscillations in the theta range (4–8Hz) are increasingly recognized as having a crucial role in flexible cognition. Such evidence is typically derived from studies in the context of reactive (stimulus-driven) control processes. However, little research has explored the role of theta oscillations in preparatory control processes. In the current study, we explored the extent of theta oscillations during proactive cognitive control and determined if these oscillations were associated with behavior. Results supported a general role of theta oscillations during proactive cognitive control, with increased power and phase coherence during the preparatory cue interval. Further, theta oscillations across frontoparietal electrodes were also modulated by proactive control demands, with increased theta phase synchrony and power for cues signaling the need for goal updating. Finally, we present novel evidence of negative associations between behavioral variability and both power and phase synchrony across many of these frontoparietal electrodes that were associated with the need for goal updating. In particular, greater consistency in frontoparietal theta oscillations, indicated by increased theta phase and power during mixed-task blocks, resulted in more consistent task-switching performance. Together, these findings provide new insight into the temporal dynamics and functional relevance of theta oscillations during proactive cognitive control.



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When Theory and Biology Differ: The Relationship Between Reward Prediction Errors and Expectancy

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Publication date: Available online 18 September 2017
Source:Biological Psychology
Author(s): Chad C. Williams, Cameron D. Hassall, Robert Trska, Clay B. Holroyd, Olave E. Krigolson
Comparisons between expectations and outcomes are critical for learning. Termed prediction errors, the violations of expectancy that occur when outcomes differ from expectations are used to modify value and shape behaviour. In the present study, we examined how a wide range of expectancy violations impacted neural signals associated with feedback processing. Participants performed a time estimation task in which they had to guess the duration of one second while their electroencephalogram was recorded. In a key manipulation, we varied task difficulty across the experiment to create a range of different feedback expectancies − reward feedback was either very expected, expected, 50/50, unexpected, or very unexpected. As predicted, the amplitude of the reward positivity, a component of the human event-related brain potential associated with feedback processing, scaled inversely with expectancy (e.g., unexpected feedback yielded a larger reward positivity than expected feedback). Interestingly, the scaling of the reward positivity to outcome expectancy was not linear as would be predicted by some theoretical models. Specifically, we found that the amplitude of the reward positivity was about equivalent for very expected and expected feedback, and for very unexpected and unexpected feedback. As such, our results demonstrate a sigmoidal relationship between reward expectancy and the amplitude of the reward positivity, with interesting implications for theories of reinforcement learning.



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Nipple sparing mastectomy and microsurgical breast reconstruction: an approach for success

Surgical management of breast cancer has evolved to allow for nipple sparing mastectomy (NSM) in oncologically eligible patients. Successful reconstruction requires complication-free execution and overall aesthetic harmony of the reconstructed and unaffected breasts. Few articles have described technical considerations and challenges encountered while performing NSM reconstruction with autologous tissue. Herein, we report our algorithm for success.

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LDT classification and therapeutic strategy of congenital body wall defects

We shared the repairing methods, which were used in our 5 cases of congenital malformations, at "The Third World Congress for Plastic Surgeons of Chinese Descent" in 2012. The title of this conference paper was "Clinical Experiences on Repairing of Huge Body Wall Defects".

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Dectin-1 is essential for IL-1β production through JNK activation and apoptosis in Aspergillus fumigatus keratitis

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Kelan Yuan, Guiqiu Zhao, Chengye Che, Cui Li, Jing Lin, Guoqiang Zhu, Kun He
PurposeTo investigate the role of phosphorylated JNK in Dectin-1-induced IL-1β production and the role of Dectin-1 in apoptosis in mouse Aspergillus fumigatus (A. fumigatus) keratitis.MethodsMice corneas were pretreated with Dectin-1 siRNA or SP600125 (the inhibitor of JNK) before A. fumigatus infection. THP-1 macrophages were preincubated with SP600125 before the stimulation of A. fumigatus conidia. Dectin-1, IL-1β, JNK, Bax, Bcl-2, cytochrome-c (cyt-c), caspase-9, caspase-8 and caspase-3 expressions were tested by PCR, Western blot, or Immunofluorescence staining.ResultsPretreatment with Dectin-1 siRNA significantly decreased A. fumigatus-induced IL-1β production and JNK phosphorylation compared with scrambled control in C57BL/6 mice corneas. SP600125 treatment before infection significantly inhibited IL-1β production compared with DMSO control both in mice corneas and THP-1 macrophages. Furthermore, Dectin-1 deficiency resulted in increased ratio of Bax/Bcl-2, release of cyt-c, activation of caspase-9 and caspase-3 in mouse A. fumigatus keratitis. However, Dectin-1 deficiency didn't affect the activation of caspase-8.ConclusionsBeing an important inflammatory PRR to mediate host inflammatory response, Dectin-1 induced IL-1β production is JNK dependent in mouse A. fumigatus keratitis, and suppressed apoptosis mediated anti-inflammatory response.



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Concurrent administration effect of antibiotic and anti-inflammatory drugs on the immunotoxicity of bacterial endotoxins

Publication date: November 2017
Source:International Immunopharmacology, Volume 52
Author(s): Azza M. El Amir, Dalia G. Tanious, Hanaa A. Mansour
Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative bacterium that causes a variety of diseases in compromised hosts. Bacterial endotoxins such as lipopolysaccharide (LPS) are the major outer surface membrane components that are present in almost all gram-negative bacteria and act as extremely strong stimulators of innate immunity and inflammation of the airway. This study was undertaken to determine the effect of combined administration of Gentamicin (GENT) as an antibiotic and Dexamethasone (DEXA) as an anti-inflammatory drug on some immunological and histological parameters. After determination of LD50 of P. aeruginosa, mice groups were injected with DEXA, GENT and lipopolysaccharide alone or in combination. Lipopolysaccharide single injection caused a significant increase of total leukocyte count, lymphocytes, neutrophils and levels of IgM and IgG. DEXA induced an increase of neutrophilia and lymphopenia. Immunological examination demonstrated that combined treatment has a significant effect of decreasing lymphocytes and IgG levels than single treatment does. Histological examination demonstrated that the inflammation of thymus, spleen, lymph node and liver decreases in mice that received combined treatment than those that received individual treatment. Concurrent administration of DEXA and GENT has a great effect on protecting organs against damage in case of endotoxemia.



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Evaluation of stopping-power prediction by dual- and single-energy computed tomography in an anthropomorphic ground-truth phantom

Publication date: Available online 17 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Patrick Wohlfahrt, Christian Möhler, Christian Richter, Steffen Greilich
PurposeTo determine the accuracy of particle range prediction for proton and heavier ion radiotherapy based on dual-energy computed tomography (DECT) in a realistic inhomogeneous geometry and to compare it to the state-of-the-art clinical approach.Methods and MaterialsA 3D ground-truth map of stopping-power ratios (SPRs) was created for an anthropomorphic head phantom by assigning measured SPR values to segmented structures in a high-resolution CT scan. This reference map was validated independently comparing proton transmission measurements to Monte Carlo transport simulations.Two DECT-based methods for direct SPR prediction via the Bethe formula (DirectSPR) and two established approaches based on Hounsfield look-up tables (HLUTs) were chosen for evaluation. SPR predictions from the four investigated methods were compared to the reference, employing material-specific voxel statistics and 2D gamma analysis. Furthermore, range deviations were analyzed in an exemplary proton treatment plan.ResultsThe established reference SPR map was successfully validated for the discrimination of SPR and range differences well below 0.3% and 1 mm respectively, even in complex inhomogeneous settings. For the phantom materials of larger volume (mainly brain, soft tissue), the investigated methods were overall able to predict SPR within 1% median deviation. The DirectSPR methods generally performed better than the HLUT approaches. For smaller phantom parts (such as cortical bone, air cavities), all methods were affected by image smoothing, leading to considerable SPR under- or overestimation. This effect was superimposed on the general SPR prediction accuracy in the exemplary treatment plan.ConclusionsDirectSPR predictions proved to be more robust with high accuracy in particular for larger volumes. In contrast, HLUT approaches exhibited a fortuitous component. The evaluation of accuracy in a realistic phantom with validated ground-truth SPR represents a crucial step towards possible clinical application of DECT-based SPR prediction methods.



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A Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities

Publication date: Available online 17 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Andrea Lo, Gareth Ayre, Roy Ma, Fred Hsu, Ryojo Akagami, Michael McKenzie, Boris Valev, Ermias Gete, Isabelle Vallieres, Alan Nichol
PurposeThe purpose of the study is to examine long-term local control of vestibular schwannoma (VS) and side effects in patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) in XX-region.Methods and MaterialsFrom August 1998 to May 2009, 207 patients were treated with radiation therapy (RT) at XX-center; 136 (66%) received SRS and 71 (34%) received SRT. Dose prescriptions were 50Gy/25 for SRT and 12Gy/1 for SRS. Our multidisciplinary provincial neuro-stereotactic conference recommended SRT for tumors >3cm and for patients with serviceable hearing (Gardner-Robertson Class I & II).ResultsMedian follow-up was 7.7 years to the last MRI and 6.4 years to the last clinical assessment. Local control for SRS vs. SRT was 94% vs. 87% at 5 years and 90% vs. 85% at 10 years (P=0.2). Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction (TND) were 25% and 25% after SRS, compared to 7% and 12% after SRT (P=0.01). Five- and 10-year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15% after SRS, vs. 13% and 15% after SRT (P=0.93). In the 49 patients with serviceable hearing at baseline who were treated with SRT, hearing preservation was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable analysis, better pre-treatment ipsilateral pure tone average was significantly associated with hearing preservation (HR 1.03; 95% CI 1.00-1.07; P=0.04).ConclusionsBoth SRS and SRT provided excellent long-term local control of VS. SRS was associated with higher rates of trigeminal nerve dysfunction. Even with a fractionated course, hearing preservation declined steadily with long-term audiometric follow-up.



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Dose escalation intensity-modulated radiotherapy–based concurrent chemoradiotherapy is effective for advanced-stage thoracic esophageal squamous cell carcinoma

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Publication date: Available online 17 September 2017
Source:Radiotherapy and Oncology
Author(s): Chia-Lun Chang, Hsieh-Chih Tsai, Wei-Cheng Lin, Jer-Hwa Chang, Han-Lin Hsu, Jyh-Ming Chow, Kevin Sheng-Po Yuan, Alexander T.H. Wu, Szu-Yuan Wu
PurposeNo studies have investigated the effects of irradiation-dose escalation intensity-modulated radiotherapy (IMRT)-based concurrent chemoradiotherapy (CCRT) in patients with thoracic esophageal squamous cell carcinoma (TESCC).Patients and methodsWe analyzed data from patients with TESCC who were enrolled in the Taiwan Cancer Registry database. To compare treatment outcomes, the patients were categorized into two groups according to their radiotherapy doses: group 1, who received CCRT<60Gy with IMRT, and group 2, who received CCRT≥60Gy with IMRT. Group 1 was used as the control for investigating posttreatment mortality risk.ResultsWe enrolled 2061 patients with TESCC without distant metastasis who received CCRT with IMRT. Multivariate Cox regression analysis indicated that advanced clinical American Joint Committee on Cancer (AJCC) stage (≥IIIA), alcohol consumption, and cigarette smoking were significant, poor independent predictors in patients with TESCC receiving IMRT-based CCRT. IMRT-based CCRT (≥60Gy; adjusted hazard ratio [aHR]: 0.75; 95% confidence interval [CI]: 0.63–0.83) was a significant independent prognostic factor for overall survival (P<0.0001). After adjustment for confounders, the aHRs (95% CIs) for overall mortality at all clinical stages were 0.75 (0.68–0.83, P<0.0001) in group 2. In group 2, the aHRs (95% CIs) for overall mortality at early (IA–IIB) and advanced (IIIA–IIIC) AJCC clinical stages were 0.89 (0.70–1.04, P=0.1905) and 0.75 (0.67–0.83, P<0.0001), respectively.ConclusionCompared with standard-dose IMRT-based CCRT, high-dose IMRT-based CCRT yields more favorable survival outcomes in patients with advanced-stage TESCC.



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A systematic review of health economic evaluation in adjuvant breast radiotherapy: Quality counted by numbers

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Publication date: Available online 17 September 2017
Source:Radiotherapy and Oncology
Author(s): Chris Monten, Liv Veldeman, Nick Verhaeghe, Yolande Lievens
BackgroundEvolving practice in adjuvant breast radiotherapy inevitably impacts healthcare budgets. This is reflected in a rise of health economic evaluations (HEE) in this domain. The available HEE literature was analysed qualitatively and quantitatively, using available instruments.MethodsHEEs published between 1/1/2000 and 31/10/2016 were retrieved through a systematic search in Medline, Cochrane and Embase. A quality-assessment using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) was translated into a quantitative score and compared with Tufts Medical Centre CEA registry and Quality of Health Economic Studies (QHES) results.ResultsTwenty cost-effectiveness analyses (CEA) and thirteen cost comparisons (CC) were analysed. In qualitative evaluation, valuation or justification of data sources, population heterogeneity and discussion on generalizability, in addition to declaration on funding, were often absent or incomplete. After quantification, the average CHEERS-scores were 74% (CI 66.9–81.1%) and 75.6% (CI 70.7–80.5%) for CEAs and CCs respectively. CEA-scores did not differ significantly from Tufts and QHES-scores.ConclusionQuantitative CHEERS evaluation is feasible and yields comparable results to validated instruments. HEE in adjuvant breast radiotherapy is of acceptable quality, however, further efforts are needed to improve comprehensive reporting of all data, indispensable for assessing relevance, reliability and generalizability of results.



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Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation

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Publication date: Available online 17 September 2017
Source:Radiotherapy and Oncology
Author(s): Xiangrong Sharon Qi, Frank Pajonk, Susan McCloskey, Daniel A. Low, Patrick Kupelian, Michael Steinberg, Ke Sheng
Background and purposeGrowing evidence suggested the coexistence of cancer stem cells (CSCs) within solid tumors. We aimed to study radiosensitivity parameters for the CSCs and differentiated tumor cells (TCs) and the correlation of the fractions of CSCs to the overall tumor radioresistance.Material and methodsSurviving fractions of breast cancer cell lines were analyzed using a dual-compartment Linear-quadratic model with independent fitting parameters: radiosensitive αTC, βTC, αCSC, βCSC, and fraction of CSCs f. The overall tumor radio-resistance, the biological effective doses and tumor control probability were estimated as a function of CSC fraction for different fractionation regimens. The pooled clinical outcome data were fitted to the single- and dual-compartment linear-quadric models.ResultsCSCs were more radioresistant characterized by smaller α compared to TCs: αTC=0.1±0.2, αCSC=0.04±0.07 for MCF-7 (f=0.1%), αTC=0.08±0.25, αCSC=0.04±0.18 for SUM159PT (f=2.46%). Higher f values were correlated with increasing radioresistance in cell lines. Analysis of clinical outcome data is in accordance of a dual-compartment CSC model prediction. Higher percentage of BCSCs resulted in more overall tumor radioresistance and less biological effectiveness.ConclusionsPercentage of CSCs strongly correlated to overall tumor radioresistance. This observation suggested potential individualized radiotherapy to account for heterogeneous population of CSCs and their distinct radiosensitivity for breast cancer.



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Comparison of multi-leaf collimator tracking and treatment-couch tracking during stereotactic body radiation therapy of prostate cancer

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Publication date: Available online 18 September 2017
Source:Radiotherapy and Oncology
Author(s): Stefanie Ehrbar, Simon Schmid, Alexander Jöhl, Stephan Klöck, Matthias Guckenberger, Oliver Riesterer, Stephanie Tanadini-Lang
Purpose and backgroundMotion mitigation during prostate stereotactic body radiation therapy (SBRT) ensures optimal target coverage while reducing the risk of overdosage of nearby organs. The geometrical and dosimetrical performance of motion mitigation with the multileaf-collimator (MLC tracking) or the treatment couch (couch tracking) were compared.Material and methodsFor ten prostate patients, SBRT treatment plans with integrated boosts were prepared using volumetric modulated arc technique. For the geometrical evaluation, a lead sphere at the beam isocenter was moved according to five prostate motion curves (i) without mitigation, (ii) with MLC tracking or (iii) with couch tracking. During irradiation, MV images were taken and the over-/underexposed areas were evaluated.For the dosimetrical evaluation, the plans were applied to a dosimetric phantom. Dose distributions with and without mitigation were evaluated inside the target structure and organs at risk.ResultsThe median over-/underexposed area was reduced significantly from 2.02cm2 without mitigation to 1.00cm2 and 0.45cm2 with MLC and couch tracking. Closest dosimetrical agreement to the static references was achieved with couch tracking.ConclusionsMLC and couch tracking at a conventional linear accelerator significantly improved the accuracy of prostate SBRT in the presence of motion, whereby couch tracking showed slightly better performance than MLC tracking.



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The Absence of an Ideal Observer: Why Some Clinical Trials May Not Be What We Think They Are.

Author: Packer, Milton MD
Page: 1085-1086


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Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke.

Author: Heller, David J. MD, MPH; Coxson, Pamela G. PhD; Penko, Joanne MS, MPH; Pletcher, Mark J. MD, MPH; Goldman, Lee MD, MPH; Odden, Michelle C. PhD, MS; Kazi, Dhruv S. MD, MS; Bibbins-Domingo, Kirsten PhD, MD, MAS
Page: 1087-1098


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When to Start a Statin Is a Preference-Sensitive Decision.

Author: Hayward, Rodney A. MD
Page: 1099-1101


http://ift.tt/2ylsN8u

Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.

Author: Krishnan, Prakash MD; Faries, Peter MD; Niazi, Khusrow MD; Jain, Ash MD; Sachar, Ravish MD; Bachinsky, William B. MD; Cardenas, Joseph MD; Werner, Martin MD; Brodmann, Marianne MD; Mustapha, J. A. MD; Mena-Hurtado, Carlos MD; Jaff, Michael R. DO; Holden, Andrew H. MD; Lyden, Sean P. MD; Mewissen, Mark; Katzen, Barry; Nanjundappa, Aravinda; Khuddus, Matheen A.; Ricci, Jason; Fry, Dennis; Shishehbor, Mehdi; Bosarge, Christopher; Kovach, Richard; Goodwin, Mark; Raja, Mohammad Laiq; Mayeda, Guy; Sandhu, Jasvinder; Rosales, Oscar; Crowder, William; Paolini, David; Henretta, John; Desai, Pratik; Farhat, Naim; Kang, Edward; Ansel, Gary; Ghani, Mohammad; Miller, William; Pollock, Christopher; Korngold, Ethan; Angle, John F.; Schultz, Greg; Gensler, Todd; Lopez, Louis; Park, James; Al-Khoury, Georges; Joels, Charles; Metzger, Christopher
Page: 1102-1113


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Long-Term Outcomes and Prognostic Factors of Complications in Takayasu Arteritis: A Multicenter Study of 318 Patients.

Author: Comarmond, Cloe MD, PhD; Biard, Lucie MPH; Lambert, Marc MD, PhD; Mekinian, Arsene MD, PhD; Ferfar, Yasmina MD; Kahn, Jean-Emmanuel MD, PhD; Benhamou, Ygal MD, PhD; Chiche, Laurent MD; Koskas, Fabien MD; Cluzel, Philippe MD, PhD; Hachulla, Eric MD, PhD; Messas, Emmanuel MD, PhD; Resche-Rigon, Matthieu MD, MPH; Cacoub, Patrice MD, PhD; Mirault, Tristan MD, PhD; Saadoun, David MD, PhD; For the French Takayasu Network
Page: 1114-1122


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Multicellular Transcriptional Analysis of Mammalian Heart Regeneration.

Author: Quaife-Ryan, Gregory A. BSc; Sim, Choon Boon PhD; Ziemann, Mark PhD; Kaspi, Antony PhD; Rafehi, Haloom PhD; Ramialison, Mirana PhD; El-Osta, Assam PhD; Hudson, James E. PhD; Porrello, Enzo R. PhD
Page: 1123-1139


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Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.

Author: Seneviratne, Anusha N. PhD *; Edsfeldt, Andreas MD, PhD *; Cole, Jennifer E. PhD +; Kassiteridi, Christina PhD +; Swart, Maarten MSc; Park, Inhye MRes, BSc; Green, Patricia Dip Hon; Khoyratty, Tariq BSc; Saliba, David PhD; Goddard, Michael E. BSc; Sansom, Stephen N. PhD; Goncalves, Isabel MD, PhD; Krams, Rob PhD; Udalova, Irina A. PhD; Monaco, Claudia MD, PhD
Page: 1140-1154


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Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment.

Author: Crea, Filippo MD; Libby, Peter MD
Page: 1155-1166


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Effects of the Selective Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin on Vascular Function and Central Hemodynamics in Patients With Type 2 Diabetes Mellitus.

Author: Striepe, Kristina MD; Jumar, Agnes MD; Ott, Christian MD; Karg, Marina V. MD; Schneider, Markus P. MD; Kannenkeril, Dennis MD; Schmieder, Roland E. MD
Page: 1167-1169


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Letter by Donzelli Regarding Article, "Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)".

Author: Donzelli, Alberto MD
Page: 1170-1171


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Letter by Koh Regarding Article, "Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)".

Author: Koh, Kwang Kon MD, PhD
Page: 1172-1173


http://ift.tt/2x9z3Tm

Response by Bress et al to Letters Regarding Article, "Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections from NHANES (National Health and Nutrition Examination Survey)".

Author: Bress, Adam P. PharmD, MS; Kramer, Holly MD, MPH; Cooper, Richard S. MD
Page: 1174-1175


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Highly selective and sensitive sensor based on an organic electrochemical transistor for the detection of ascorbic acid

Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Lijun Zhang, Guiheng Wang, Di Wu, Can Xiong, Lei Zheng, Yunsheng Ding, Hongbo Lu, Guobing Zhang, Longzhen Qiu
In this study, an organic electrochemical transistor sensor (OECT) with a molecularly imprinted polymer (MIP)-modified gate electrode was prepared for the detection of ascorbic acid (AA). The combination of the amplification function of an OECT and the selective specificity of MIPs afforded a highly sensitive, selective OECT sensor. Cyclic voltammetry and electrochemical impedance spectroscopy measurements were carried out to monitor the stepwise fabrication of the modified electrodes and the adsorption capacity of the MIP/Au electrodes. Atomic force microscopy was employed for examining the surface morphology of the electrodes. Important detection parameters, pH and detection temperature were optimized. With the change in the relative concentration of AA from 1μM to 100μM, the MIP-OECT sensor exhibited a low detection limit of 10nM (S/N>3) and a sensitivity of 75.3μA channel current change per decade under optimal conditions. In addition, the MIP-OECT sensor exhibited excellent specific recognition ability to AA, which prevented the interference from other structurally similar compounds (e.g., aspartic acid, glucose, uric acid, glycine, glutathione, H2O2), and common metal ions (K+, Na+, Ca2+, Mg2+, and Fe2+). In addition, a series of vitamin C beverages were analyzed to demonstrate the feasibility of the MIP-OECT sensor. Using the proposed principle, several other sensors with improved performance can be constructed via the modification of organic electrochemical transistors with appropriate MIP films.

Graphical abstract

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Preparation, characterization and application of urease nanoparticles for construction of an improved potentiometric urea biosensor

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Publication date: 15 February 2018
Source:Biosensors and Bioelectronics, Volume 100
Author(s): Seema Jakhar, C.S. Pundir
The nanoparticles (NPs) aggregates of commercial urease from jack beans (Canavalia ensiformis) were prepared by desolvation and glutaraldehyde crosslinking and functionalized by cysteamine dihydrochloride. These enzyme nanoparticles (ENPs) were characterized by transmission electron microscopy (TEM), UV and Fourier transform infrared (FTIR) spectroscopy. The TEM images of urease NPs showed their size in the range, 18–100nm with an average of 51.2nm. The ENPs were more active and stable with a longer shelf life than native enzyme molecules. The ENPs were immobilized onto chitosan (CHIT) activated nitrocellulose (NC) membrane via glutaraldehyde coupling with 32.22% retention of initial activity of free urease NPs with a conjugation yield of 1.63mg/cm2. This NC membrane was mounted at the lower/sensitive end of the ammonium ion selective electrode (AISE) with O-ring and then electrode was connected to a digital pH meter to construct a potentiometric urea biosensor. The biosensor exhibited optimum response within 10s at pH 5.5 and 40°C. The biosensor was employed for measurement of potentiometric determination of urea in sera of apparently healthy and persons suffering from kidney disorders. The biosensor displayed a low detection limit of 1µM/L with a wide working range of 2–80µM/L (0.002–0.08mM) and sensitivity of 23mV/decade. The analytical recovery of added urea in serum was 106.33%. The within and between-batch coefficient of variations (CVs) of present biosensor were 0.18% and 0.32% respectively. There was a good correlation (r = 0.99) between sera urea values obtained by reference method (Enzymic colorimetric kit method) and the present biosensor. The biosensor had negligible interference from Na+,K+,NH+4 and Ca2+ but Mg2+,Cu2+ and ascorbic acid but had slight interference, which was overcome by specific ion selective electrode. The ENPs bound NC membrane was used maximally 8–9 times per day over a period of 180 days, when stored in 0.01M sodium acetate buffer pH 5.5 at 4°C.



http://ift.tt/2f6hQ2b

Texture and art with deep neural networks

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Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Leon A .Gatys, Alexander S Ecker, Matthias Bethge
Although the study of biological vision and computer vision attempt to understand powerful visual information processing from different angles, they have a long history of informing each other. Recent advances in texture synthesis that were motivated by visual neuroscience have led to a substantial advance in image synthesis and manipulation in computer vision using convolutional neural networks (CNNs). Here, we review these recent advances and discuss how they can in turn inspire new research in visual perception and computational neuroscience.



http://ift.tt/2xtT4U7

Predicting preschool children's eating in the absence of hunger from maternal pressure to eat: A longitudinal study of low-income, Latina mothers

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Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Lionor Galindo, Thomas G. Power, Ashley D. Beck, Jennifer Orlet Fisher, Teresia M. O'Connor, Sheryl O. Hughes
Early work by Klesges et al. (1983, 1986) suggested that mothers who frequently prompt their children to eat have children at greater risk for obesity. This is consistent with the hypothesis that controlling feeding practices override children's responsiveness to their internal fullness cues, increasing the risk of overeating and obesity (e.g., Johnson & Birch, 1994). Subsequent cross-sectional research on pressure to eat, however, has been inconsistent. Most studies have shown that maternal self-reports of pressure to eat are negatively associated with childhood obesity, and observational studies showed inconsistent relationships with child weight status. In the present study we examined the association between low-income, Latina mothers' pressure to eat and their preschool children's eating in the absence of hunger using both self-report and observational measures of feeding practices. A longitudinal design examined eating in the absence of hunger over 18 months; children's BMI at the initial timepoint was statistically controlled to address the tendency of mothers of underweight children to pressure their children to eat. At each timepoint, mothers completed the Child Feeding Questionnaire (Birch et al., 2001) and were observed feeding their child a meal in a laboratory setting. Eating in the absence of hunger (Fisher & Birch, 1999) was assessed at both timepoints as well. A cross-lagged panel model showed that observed maternal prompts to eat a different food at time one predicted kcal consumed in the absence of hunger at time two (controlling for kcal consumed in the absence of hunger at first timepoint: beta = 0.20, p < 0.05). Results suggest that pressure to eat alone may not be what contributes to eating in the absence of hunger, but that the nature of that pressure may be more important.



http://ift.tt/2wBWWi3

Characterization of PM 2.5 in Delhi: role and impact of secondary aerosol, burning of biomass, and municipal solid waste and crustal matter

Abstract

Delhi is one among the highly air polluted cities in the world. Absence of causal relationship between emitting sources of PM2.5 and their impact has resulted in inadequate actions. This research combines a set of innovative and state-of-the-art analytical techniques to establish relative predominance of PM2.5 sources. Air quality sampling at six sites in summer and winter for 40 days (at each site) showed alarmingly high PM2.5 concentrations (340 ± 135 μg/m3). The collected PM2.5 was subjected to chemical speciation including ions, metals, organic and elemental carbons which followed application of chemical mass balance technique for source apportionment. The source apportionment results showed that secondary aerosols, biomass burning (BMB), vehicles, fugitive dust, coal and fly ash, and municipal solid waste burning were the important sources. It was observed that secondary aerosol and crustal matter accounted for over 50% of mass. The PM2.5 levels were not solely result of emissions from Delhi; it is a larger regional problem caused by contiguous urban agglomerations. It was argued that emission reduction of precursors of secondary aerosol, SO2, NOx, and volatile organic compounds, which are unabated, is essential. A substantial reduction in BMB and suspension of crustal dust is equally important to ensure compliance with air quality standards.



http://ift.tt/2fgzFiM

Sediment core data reconstruct the management history and usage of a heavily modified urban lake in Berlin, Germany

Abstract

Urban surface waters face several stressors associated with industry and urban water management. Over much of the past century, the wastewater treatment in Berlin, Germany, relied on inefficient sewage farms, which resulted in severe eutrophication and sediment contamination in the recipient surface waterbodies. A prominent example is Lake Tegel, where a multitude of management measures were applied in the last decades for the purpose of ecosystem restoration. In this study, we analyzed sediment cores of three lakes with X-ray fluorescence spectroscopy: Lake Tegel, Lake Großer Wannsee, which is environmentally similar but has a different management history, and Lake Userin, which serves as a reference located in a nature protection area. Multivariate statistical methods (principal component analysis, k-means clustering, and self-organizing maps) were used to assess the sediment quality and to reconstruct the management history of Lake Tegel. Principal component analysis established two main gradients of sediment composition: heavy metals and lithogenic elements. The impact of the management measures was visualized in the lake sediment composition changing from high abundance of heavy metals and reducing redox conditions to less-impacted sediments in recent layers. The clustering techniques suggested heterogeneity among sites within Lake Tegel that probably reflect urban water management measures. The abundance of heavy metals in recent lake sediments of Lake Tegel is similar to a lake with low urban impact and is lower than in Lake Großer Wannsee suggesting that the management measures were successful in the reduction of heavy metals, which are still a threat for surface waters worldwide.



http://ift.tt/2xsWfeP

Volumetric and linear changes at dental implants following grafting with volume-stable three-dimensional collagen matrices or autogenous connective tissue grafts: 6-month data

Abstract

Objectives

The objective of this study was to test whether or not soft tissue augmentation with a volume-stable collagen matrix (VCMX) leads to similar volume gain around dental implants compared to autogenous subepithelial connective tissue graft (SCTG).

Materials and methods

In 12 adult beagle dogs, immediate implants were placed with simultaneous guided bone regeneration. After 25–45 weeks, soft tissue augmentation was randomly performed using VCMX, SCTG, or a sham-operated control. Impressions were taken pre-op and post-op (tissue augmentation) and again at sacrifice after healing periods of 4, 8, and 24 weeks. They were then digitized to allow for superimposition. Values of linear and volumetric changes were calculated.

Results

The median increase (pre-op to post-op) in buccal volume measured 0.92 mm for VCMX, 1.47 mm for SCTG, and 0.24 mm for SH. The values (pre-op to sacrifice) were − 0.25 mm for VCMX, 0.52 mm for SCTG, and − 0.06 mm for group SH. The median ridge width 2 mm below the crest measured − 0.26 mm for VCMX, 0.53 mm for SCTG, and − 0.15 mm for SH (pre-op to sacrifice).

Conclusions

Volume augmentation using VCMX and SCTG resulted in an increase in ridge dimension (pre- to post-op). During the follow-up, the volume decreased in all three groups to a level close to the situation prior to surgery.

Clinical relevance

Soft tissue volume augmentation around dental implants is usually performed using the patient's own tissue. This therapy is associated with an increased morbidity due to a second surgical site. Soft tissue volume at implant sites can be augmented using VCMX and SCTG. The gain on top of the ridge appears not to be stable during the follow-up in both groups.



http://ift.tt/2fg7v7P

Investigating the behavior of binding properties between dissolved organic matter (DOM) and Pb(II) during the soil sorption process using parallel factor analysis (PARAFAC) and two-dimensional correlation spectroscopy (2D-COS)

Abstract

Dissolved organic matter (DOM) is the most active component in an environmental system. It can influence the chemical and structural characteristics of soil. In this work, three-dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy, parallel factor analysis (PARAFAC), and two-dimensional correlation spectroscopy (2D-COS) integrated with synchronous fluorescence were used to explore the interaction between soil-derived DOM and Pb(II) during the soil sorption process. According to the data of batch sorption experiments, the adsorbing capacities of soil, soil + 5 mL DOM, and soil + 10 mL DOM were 16.96, 18.29, and 19.32 mg g−1, respectively, which indicated that DOM significantly enhanced the adsorption efficiency of Pb(II). The pseudo-second-order kinetic equation could well explain the adsorption process. The adsorbing data conformed to the isotherm of Langmuir adsorption. According to EEM-PARAFAC results, there are two major components from DOM. Protein-like substances were represented by component 1, and humic-like and fulvic-like substances were represented by component 2. Based on 3D-EEM, the results further showed that the intensities of component 1 and component 2 were obviously quenched with the increase of Pb(II) concentrations. The combined interpretations of the 2D-COS map for the DOM revealed that Pb(II) binding might occur sequentially in the order of humic-like fraction > protein-like fraction (346 > 282 nm). According to synchronous fluorescence spectra, static fluorescence quenching was the major process of quenching.

Graphical abstract



http://ift.tt/2ylLMA7

Effects of a hypothetical escape of CO 2 gas from subterranean storage sites on water flea Daphnia magna

Abstract

The impacts of a hypothetical CO2 gas leak from freshwater sediments on the survival and reproduction of freshwater flea Daphnia magna were analyzed. Another objective was to assess the performance of standard toxicity testing protocols for CO2-induced acidification research in freshwaters. Four pH levels (7.5, 7.0, 6.5, and 6.0) and two sediments with different contamination level were tested. The results revealed that the D. magna are susceptible to a gradual but relatively rapid CO2 enrichment of the water column causing a change from circumneutral to acidic conditions. Standard 48-h immobilization test with D. magna tended to underestimate the toxicity at CO2-induced acidity condition. Dissolved aluminum may be implicated in the toxicity to the parental daphnids exposed. Metal outflux from sediments and behavior in elutriate have been discussed.



http://ift.tt/2ym4c3A

Hydrogen fluoride (HF) substance flow analysis for safe and sustainable chemical industry

Abstract

In this study, the chemical substance flow of hydrogen fluoride (hydrofluoric acid, HF) in domestic chemical industries in 2014 was analyzed in order to provide a basic material and information for the establishment of organized management system to ensure safety during HF applications. A total of 44,751 tons of HF was made by four domestic companies (in 2014); import amount was 95,984 tons in 2014 while 21,579 tons of HF was imported in 2005. The export amount of HF was 2180 tons, of which 2074 ton (China, 1422 tons, U.S. 524 tons, and Malaysia, 128 tons) was exported for the manufacturing of semiconductors. Based on the export and import amounts, it can be inferred that HF was used for manufacturing semiconductors. The industries applications of 161,123 tons of HF were as follows: manufacturing of basic inorganic chemical substance (27,937 tons), manufacturing of other chemical products such as detergents (28,208 tons), manufacturing of flat display (24,896 tons), and manufacturing of glass container package (22,002 tons). In this study, an analysis of the chemical substance flow showed that HF was mainly used in the semiconductor industry as well as glass container manufacturing. Combined with other risk management tools and approaches in the chemical industry, the chemical substance flow analysis (CSFA) can be a useful tool and method for assessment and management. The current CSFA results provide useful information for policy making in the chemical industry and national systems.

Graphical abstract

Hydrogen fluoride chemical substance flows in 2014 in South Korea.


http://ift.tt/2wpEmOB

A review on the mechanism, risk evaluation, and prevention of coal spontaneous combustion in China

Abstract

In recent years, the ecology, security, and sustainable development of modern mines have become the theme of coal mine development worldwide. However, spontaneous combustion of coal under conditions of oxygen supply and automatic exothermic heating during coal mining lead to coalfield fires. Coal spontaneous combustion (CSC) causes huge economic losses and casualties, with the toxic and harmful gases produced during coal combustion not only polluting the working environment, but also causing great damage to the ecological environment. China is the world's largest coal producer and consumer; however, coal production in Chinese mines is seriously threatened by the CSC risk. Because deep underground mining methods are commonly adopted in Chinese coal mines, coupling disasters are frequent in these mines with the coalfield fires becoming increasingly serious. Therefore, in this study, we analyzed the development mechanism of CSC. The CSC risk assessment was performed from the aspects of prediction, detection, and determination of the "dangerous area" in a coal mine (i.e., the area most susceptible to fire hazards). A new geophysical method for CSC determination is proposed and analyzed. Furthermore, the main methods for CSC fire prevention and control and their advantages and disadvantages are analyzed. To eventually construct CSC prevention and control integration system, future developmental direction of CSC was given from five aspects. Our results can present a reference for the development of CSC fire prevention and control technology and promote the protection of ecological environment in China.



http://ift.tt/2wqRtiD

Title page/Editorial Board

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Publication date: September 2017
Source:Medical Hypotheses, Volume 107





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U isotopes distribution in the Lower Rhone River and its implication on radionuclides disequilibrium within the decay series

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Mathilde Zebracki, Xavier Cagnat, Stéphanie Gairoard, Nicolas Cariou, Frédérique Eyrolle-Boyer, Béatrice Boulet, Christelle Antonelli
The large rivers are main pathways for the delivery of suspended sediments into coastal environments, affecting the biogeochemical fluxes and the ecosystem functioning. The radionuclides from 238U and 232Th—series can be used to understand the dynamic processes affecting both catchment soil erosion and sediment delivery to oceans. Based on annual water discharge the Rhone River represents the largest river of the Mediterranean Sea. The Rhone valley also represents the largest concentration in nuclear power plants in Europe. A radioactive disequilibrium between particulate 226Ra(p) and 238U(p) was observed in the suspended sediment discharged by the Lower Rhone River (Eyrolle et al. 2012), and a fraction of particulate 234Th was shown to derive from dissolved 238U(d) (Zebracki et al. 2013). This extensive study has investigated the dissolved U isotopes distribution in the Lower Rhone River and its implication on particulate radionuclides disequilibrium within the decay series. The suspended sediment and filtered river waters were collected at low and high water discharges. During the 4—months of the study, two flood events generated by the Rhone southern tributaries were monitored. In river waters, the total U(d) concentration and U isotopes distribution were obtained through Q-ICP-MS measurements. The Lower Rhone River has displayed non-conservative U—behavior, and the variations in U(d) concentration between southern tributaries were related to the differences in bedrock lithology. The artificially occurring 236U was detected in the Rhone River at low water discharges, and was attributed to the liquid releases from nuclear industries located along the river. The (235U/238U)(d) activity ratio (=AR) in river waters was representative of the 235U natural abundance on Earth. The (226Ra/238U)(p) AR in suspended sediment has indicated a radioactive disequilibrium (average 1.3 ± 0.1). The excess of 234Th in suspended sediment =(234Thxs(p)) was apparent solely at low water discharges. The activity of 234Thxs(p) was calculated through gamma measurements and ranged from unquantifiable to 56 ± 14 Bq kg−1. The possibility of using 234Th as a tracer for the suspended sediment dynamics in large Mediterranean river was then discussed.



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The NCDR ICD Registry: A Foundation for Quality Improvement



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Histopathological and Immunological Characteristics of Tachycardia-Induced Cardiomyopathy



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Adherence Tradeoff to Multiple Preventive Therapies and All-Cause Mortality After Acute Myocardial Infarction

AbstractBackground

Angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB), beta-blockers and statins are recommended after acute myocardial infarction (AMI). Patients may adhere to some, but not all, therapies.

Objectives

The authors investigated the effect of tradeoffs in adherence to ACE inhibitors/ARBs, beta-blockers, and statins on survival among older people after AMI.

Methods

The authors identified 90,869 Medicare beneficiaries ≥65 years of age who had prescriptions for ACE inhibitors/ARBs, beta-blockers, and statins, and survived ≥180 days after AMI hospitalization in 2008 to 2010. Adherence was measured by proportion of days covered (PDC) during 180 days following hospital discharge. Mortality follow-up extended up to 18 months after this period. The authors used Cox proportional hazards models to estimate hazard ratios of mortality for groups adherent to 2, 1, or none of the therapies versus group adherent to all 3 therapies.

Results

Only 49% of the patients adhered (PDC ≥80%) to all 3 therapies. Compared with being adherent to all 3 therapies, multivariable-adjusted hazard ratios (95% confidence intervals [CIs]) for mortality were 1.12 (95% CI: 1.04 to 1.21) for being adherent to ACE inhibitors/ARBs and beta-blockers only, 0.98 (95% CI: 0.91 to 1.07) for ACEI/ARBs and statins only, 1.17 (95% CI: 1.10 to 1.25) beta-blockers and statins only, 1.19 (95% CI: 1.07 to 1.32) for ACE inhibitors/ARBs only, 1.32 (95% CI: 1.21 to 1.44) for beta-blockers only, 1.26 (95% CI: 1.15 to 1.38) statins only, and 1.65 (95% CI: 1.54 to 1.76) for being nonadherent (PDC <80%) to all 3 therapies.

Conclusions

Patients adherent to ACE inhibitors/ARBs and statins only had similar mortality rates as those adherent to all 3 therapies, suggesting limited additional benefit for beta-blockers in patients who were adherent to statins and ACE inhibitors/ARBs. Nonadherence to ACE inhibitors/ARBs and/or statins was associated with higher mortality.



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Reducing Arterial Stiffness Independently of Blood Pressure: The VaSera Trial



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"Sticky" Issues for Adherence in Secondary Prevention



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A Test in Context: Lipid Profile, Fasting Versus Nonfasting

Abstract

Fasting for >8 h, as previously required for lipid profiles, normally only occurs a few hours before breakfast. By contrast, the nonfasting state predominates most of a 24-h cycle and better captures atherogenic lipoprotein levels. Plasma contains atherogenic lipoproteins of hepatic origin in the fasting state and additionally those of intestinal origin in the nonfasting state. Maximal mean changes for random, nonfasting versus fasting levels are +26 mg/dl for triglycerides, –8 mg/dl for total cholesterol, –8 mg/dl for low-density lipoprotein cholesterol, +8 mg/dl for remnant cholesterol, and –8 mg/dl for non–high-density lipoprotein cholesterol; lipoprotein(a), apolipoprotein B, and high-density lipoprotein cholesterol are largely unaffected. For patients, laboratories, and clinicians alike, nonfasting lipid profiles represent a simplification without negative implications for prognostic, diagnostic, and therapeutic options for cardiovascular disease prevention. Several societies' guidelines and statements in Denmark, the United Kingdom, Europe, Canada, Brazil, and the United States endorse nonfasting lipid profiles.



http://ift.tt/2ykG4ym

Effect of Definition on Incidence and Prognosis of Type 2 Myocardial Infarction

AbstractBackground

Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice.

Objectives

This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need.

Methods

The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI2007); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI2012).

Results

Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI2007 definition was 2.8% (n = 112). The application of the more liberal T2MI2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI2012reclassified). Among T2MI2007, 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI2012reclassified, which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI2012reclassified vs. T2MI2007 and T1MI: p = 0.03 and 0.01, respectively).

Conclusions

T2MI2012reclassified has a substantially lower event-related mortality rate compared with T2MI2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587)



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Application of the Statin-Associated Muscle Symptoms-Clinical Index to a Randomized Trial on Statin Myopathy



http://ift.tt/2ykPkSQ

The Many Faces of Type 2 Myocardial Infarction



http://ift.tt/2ykIgpt

{beta}-Blockers and Outcome After Acute Myocardial Infarction



http://ift.tt/2ykXHOn

Persistence With Dabigatran Therapy at 2 Years in Patients With Atrial Fibrillation

AbstractBackground

Guidelines recommend long-term oral anticoagulation therapy for stroke prevention in patients with atrial fibrillation (AF). Treatment discontinuation rates in vitamin K antagonist (VKA)-treated patients are high but may be lower with non-VKA oral anticoagulant agents.

Objectives

The goal of this study was to describe and explore predictors of dabigatran etexilate persistence in patients with newly diagnosed AF over 2 years of follow-up.

Methods

Consecutive patients newly diagnosed with AF and ≥1 stroke risk factor were followed up for 2 years. Dabigatran nonpersistence was defined as discontinuation of dabigatran for >30 days. A multivariable Cox regression model included region as well as patient clinical and sociodemographic characteristics to explore predictors of nonpersistence.

Results

Eligible patients (N = 2,932) took ≥1 dabigatran dose; their mean age was 70.3 ± 10.2 years, and 55.3% were male. The 2-year probability of dabigatran persistence was 69.2%. Approximately 7% switched to a factor Xa inhibitor and 6% to a VKA. Approximately one-third of dabigatran discontinuations were primarily due to serious or nonserious adverse events. Patients from North America had the highest discontinuation risk, and Latin America had the lowest. Minimally symptomatic or asymptomatic AF and permanent AF were associated with a lower risk for dabigatran nonpersistence. Previous proton pump inhibitor use was associated with a higher risk for dabigatran nonpersistence.

Conclusions

Probability of treatment persistence with dabigatran after 2 years was approximately 70%. Nearly one-half of the patients who stopped dabigatran switched to another oral anticoagulant agent. Patients from North America, and those with paroxysmal, persistent, or symptomatic AF, may be at a higher risk for discontinuing dabigatran.



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JACC Instructions for Authors



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Pills Never Work in the Bottle



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ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for C



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Inferior Vena Cava Filters to Prevent Pulmonary Embolism: Systematic Review and Meta-Analysis

AbstractBackground

Inferior vena cava (IVC) filters are widely used for prevention of pulmonary embolism (PE). However, uncertainty persists about their efficacy and safety.

Objectives

The authors conducted a systematic review and meta-analysis of the published reports on the efficacy and safety of IVC filters.

Methods

The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through October 3, 2016, for randomized controlled trials (RCTs) or prospective controlled observational studies of IVC filters versus none in patients at risk of PE. Inverse variance fixed-effects models with odds ratio (OR) as the effect measure were used for primary analyses. Main outcomes included subsequent PE, PE-related mortality, all-cause mortality, and subsequent deep vein thrombosis (DVT).

Results

The authors' search retrieved 1,986 studies, of which 11 met criteria for inclusion (6 RCTs and 5 prospective observational studies). Quality of evidence for RCTs was low to moderate. Overall, patients receiving IVC filters had lower risk for subsequent PE (OR: 0.50; 95% confidence interval [CI]: 0.33 to 0.75); increased risk for DVT (OR: 1.70; 95% CI: 1.17 to 2.48); nonsignificantly lower PE-related mortality (OR: 0.51; 95% CI: 0.25 to 1.05); and no change in all-cause mortality (OR: 0.91; 95% CI: 0.70 to 1.19). Limiting the results to RCTs showed similar results. Findings were substantively similar across a wide range of sensitivity analyses.

Conclusions

Very few prospective controlled studies, with limited quality of evidence, exist regarding the efficacy and safety of IVC filters. Overall, filters appear to reduce the risk of subsequent PE, increase the risk for DVT, and have no significant effect on overall mortality.



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Preparing Fellows for Precision Cardiology: Are We Ready?



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The Elusive Evidence for Inferior Vena Cava Filters to Prevent Pulmonary Embolism



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Patients With an ICD Remain at Risk for Painful Shocks in Last Moments of Life



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Bone Marrow-Derived Tenascin-C Attenuates Cardiac Hypertrophy by Controlling Inflammation

AbstractBackground

Tenascin-C (TNC) is a highly conserved matricellular protein with a distinct expression pattern during development and disease. Remodeling of the left ventricle (LV) in response to pressure overload leads to the re-expression of the fetal gene program.

Objectives

The aim of this study was to investigate the function of TNC in cardiac hypertrophy in response to pressure overload.

Methods

Pressure overload was induced in TNC knockout and wild-type mice by constricting their abdominal aorta or by infusion of angiotensin II. Echocardiography, immunostaining, flow cytometry, quantitative real-time polymerase chain reaction, and reciprocal bone marrow transplantation were used to evaluate the effect of TNC deficiency.

Results

Echocardiographic analysis of pressure overloaded hearts revealed that all LV parameters (LV end-diastolic and -systolic dimensions, ejection fraction, and fractional shortening) deteriorated in TNC-deficient mice compared with their wild-type counterparts. Cardiomyocyte size and collagen accumulation were significantly greater in the absence of TNC. Mechanistically, TNC deficiency promoted rapid accumulation of the CCR2+/Ly6Chi monocyte/macrophage subset into the myocardium in response to pressure overload. Further, echocardiographic and immunohistochemical analyses of recipient hearts showed that expression of TNC in the bone marrow, but not the myocardium, protected the myocardium against excessive remodeling of the pressure-overloaded heart.

Conclusions

TNC deficiency further impaired cardiac function in response to pressure overload and exacerbated fibrosis by enhancing inflammation. In addition, expression of TNC in the bone marrow, but not the myocardium, protected the myocardium against excessive remodeling in response to mild pressure overload.



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Outcomes of TAVR in Bicuspid Aortic Valve Stenosis



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Immunomodulation in multiple sclerosis: promises and pitfalls

Publication date: December 2017
Source:Current Opinion in Immunology, Volume 49
Author(s): Calliope A Dendrou, Lars Fugger
Multiple sclerosis (MS) afflicts about 2.5 million people globally and poses a major personal and socioeconomic burden. The recognition of MS as an inflammatory disease, characterized by infiltration of immune cells into the central nervous system, has spurred research into the autoimmune etiology of the condition and has provided the rationale for its treatment through immunomodulation. Experience with immunotherapies in MS to date has suggested a disparity between the observed immune cell infiltration and the progressive loss of neurons. However, recent clinical efforts are providing new insights into progressive MS that once again place the immune system at center stage. This article reviews the main mechanisms of MS immunopathogenesis, and the benefits, risks and challenges of immunomodulatory treatments for the disease.



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In situ gold-nanoparticle electrogeneration on gold films deposited on paper for non-enzymatic electrochemical determination of glucose

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Estefanía Núnez-Bajo, M. Carmen Blanco-López, Agustín Costa-García, M. Teresa Fernández-Abedul
This work describes the development and evaluation of a new electrochemical platform based on the sustainable generation of gold-nanoparticles on paper-based gold-sputtered electrodes. The disposable porous paper electrode is combined with screen-printed electrodes for ensuring a precise electrogeneration of nanoparticles and also for the evaluation of these simple, versatile and low-cost microfluidic devices. Two types of chromatographic paper with different thicknesses have been evaluated. Paper gold working electrodes modified with gold nanoparticles were characterized by scanning electron microscopy and cyclic voltammetry using potassium ferrocyanide as a common redox probe, showing an improved electrochemical performance when compared to bare gold electrodes. The platform has been applied to the non-enzymatic determination of glucose, molecule of enormous interest. The porous gold structure made by sputtering on paper, modified with electrogenerated nanoparticles allowed precise and accurate determination of the analyte in beverages at low potential.

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An approach for quantification of platinum distribution in tissues by LA-ICP-MS imaging using isotope dilution analysis

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): I. Moraleja, M.L. Mena, A. Lázaro, B. Neumann, A. Tejedor, N. Jakubowski, M.M. Gómez-Gómez, D. Esteban-Fernández
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been revealed as a convenient technique for trace elemental imaging in tissue sections, providing elemental 2D distribution at a quantitative level. For quantification purposes, in the last years several approaches have been proposed in the literature such as the use of CRMs or matrix matched standards. The use of Isotope Dilution (ID) for quantification by LA-ICP-MS has been also described, being mainly useful for bulk analysis but not feasible for spatial measurements so far. In this work, a quantification method based on ID analysis was developed by printing isotope-enriched inks onto kidney slices from rats treated with antitumoral Pt-based drugs using a commercial ink-jet device, in order to perform an elemental quantification in different areas from bio-images. For the ID experiments 194Pt enriched platinum was used. The methodology was validated by deposition of natural Pt standard droplets with a known amount of Pt onto the surface of a control tissue, where could be quantified even 50pg of Pt, with recoveries higher than 90%. The amount of Pt present in the whole kidney slices was quantified for cisplatin, carboplatin and oxaliplatin-treated rats. The results obtained were in accordance with those previously reported. The amount of Pt distributed between the medullar and cortical areas was also quantified, observing different behavior for the three drugs.

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Highly selective detection of phosphate ion based on a single-layered graphene quantum dots-Al3+ strategy

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): Bin Bin Chen, Rong Sheng Li, Meng Li Liu, Hong Yan Zou, Hui Liu, Cheng Zhi Huang
Determination of phosphate ion (PO43-) is important in biomedical and environmental arrays because its controlling concentrations are associated with different pathologies or the quality of water. Herein, we report a new type of photoluminescence (PL) probe for highly selective detection of PO43- based on a single-layered graphene quantum dots chelating with aluminium ions (s-GQDs-Al3+) system. The PL of s-GQDs can be enhanced by Al3+ through the aggregation-induced emission enhancement (AIEE) effect. With the addition of PO43-, the PL of the s-GQDs-Al3+ system is faded away because PO43- has stronger coordination with Al3+ which results in the elimination of AIEE effect and the decrease in the PL intensity of the s-GQDs-Al3+ system. Therefore, the s-GQDs-Al3+ system can behave as an on-off type PL probe for PO43- detection. It is found that the PL intensity ratio (I/I0) of s-GQDs in the presence of Al3+ at 463nm is proportional to the concentration of PO43- in the range of 0.25–7.5μM with the limit of detection as low as 0.1μM. This selective assay has a great application prospect in the complex matrixes owing to its simplicity and specificity for PO43- detection.

Graphical abstract

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Prediction of parameters related to grape ripening by multivariate calibration of voltammetric signals acquired by an electronic tongue

Publication date: 1 February 2018
Source:Talanta, Volume 178
Author(s): L. Pigani, G. Vasile Simone, G. Foca, A. Ulrici, F. Masino, L. Cubillana-Aguilera, R. Calvini, R. Seeber
An electronic tongue (ET) consisting of two voltammetric sensors, namely a poly-ethylendioxythiophene modified Pt electrode and a sonogel carbon electrode, has been developed aiming at monitoring grape ripening. To test the effectiveness of device and measurement procedures developed, samples of three varieties of grapes have been collected from veraison to harvest of the mature grape bunches. The derived musts have been then submitted to electrochemical investigation using Differential Pulse Voltammetry technique. At the same time, quantitative determination of specific analytical parameters for the evaluation of technological and phenolic maturity of each sample has been performed by means of conventional analytical techniques. After a preliminary inspection by principal component analysis, calibration models were calculated both by partial least squares (PLS) on the whole signals and by the interval partial least squares (iPLS) variable selection algorithm, in order to estimate physico-chemical parameters. Calibration models have been obtained both considering separately the signals of each sensor of the ET, and by proper fusion of the voltammetric data selected from the two sensors by iPLS. The latter procedure allowed us to check the possible complementarity of the information brought by the different electrodes. Good predictive models have been obtained for estimation of pH, total acidity, sugar content, and anthocyanins content. The application of the ET for fast evaluation of grape ripening and of most suitable harvesting time is proposed.

Graphical abstract

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Strontium and magnesium ions released from bioactive titanium metal promote early bone bonding in a rabbit implant model

Publication date: Available online 14 September 2017
Source:Acta Biomaterialia
Author(s): Yaichiro Okuzu, Shunsuke Fujibayashi, Seiji Yamaguchi, Koji Yamamoto, Takayoshi Shimizu, Takashi Sono, Koji Goto, Bungo Otsuki, Tomiharu Matsushita, Tadashi Kokubo, Shuichi Matsuda
We have previously developed the "alkali and heat treatment" method to confer bioactivity (bone-bonding ability) to titanium metal (Ti). As strontium (Sr) and magnesium (Mg) ions reportedly promote osteoblastic cell proliferation and differentiation and accelerate bone formation, we improved this method to induce the release of Sr (Sr-Ti) or Mg (Mg-Ti) ions from Ti in a previous study. Here, we evaluated the bioactivity of these novel surface treatments, Sr-Ti and Mg-Ti. In vitro evaluation of cell viability, expression of integrin β1, β catenin, and cyclin D1, osteogenic gene expression, alkaline phosphatase activity, and extracellular mineralization using MC3T3-E1 cells revealed that Sr-Ti and Mg-Ti enhanced proliferation and osteogenic differentiation. In rabbit in vivo studies, Sr-Ti and Mg-Ti also provided greater biomechanical strength and bone-implant contact than the positive control Ti (Ca-Ti), especially at the early stage (4–8 weeks), and maintained these properties for a longer period (16–24 weeks). Advantages of the improved method include process simplicity, applicability for any implant shape, and lack of adverse effects on implant composition and structure. Therefore, our treatment is promising for clinical applications to achieve early bone bonding.Statement of SignificanceImplantation into osteoporotic bone constitutes a challenging problem because of early migration or loosening of the implant, which is primarily due to insufficient initial fixation in porotic bone. Therefore, it is desirable to provide implants with a capacity for early bone bonding. We have achieved conferring early bone bonding ability to titanium metal by releasing strontium ions or magnesium ions. Our treatment is promising for clinical applications to achieve early bone bonding of orthopedic or dental Ti-based implants.

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A Raman spectroscopic investigation of the mechanism of the reduction of hair with thioglycerol and the accompanying disulfide conformational changes

Abstract

Objective

The objective of our research was to investigate the reduction mechanism of thioglycerol (TG) on hair keratin fibres.

Methods

The structure of cross-sections at various depths of virgin white human hair resulting from the permanent waving process with TG was directly analyzed at the molecular level using Raman spectroscopy. Also, the penetration of TG for the cross-sectional samples dyed with methylene blue was observed by optical microscopy.

Results

The gauche-gauche-gauche (GGG) and gauche-gauche-trans (GGT) conformations of disulfide (–SS–) groups remarkably decreased, while the trans-gauche-trans (TGT) conformation increased by performing the reduction process with TG. In addition, the disconnected –SS– content at various depths of the hair sample reduced with TG adjusted to pH 9.0 with ammonia solution, was clearly increased compared with that of the hair sample reduced with TG adjusted to pH 9.0 with monoethanolamine. In the case of adjusting to pH 9.0 with ammonia solution, the tensile strength of the waved hair treated with TG was strong compared with that of the waved hair treated with thioglycolic acid (TGA), but the waving efficiency of the waved hair treated with TG was nevertheless higher than that of the waved hair treated with TGA.

Conclusion

The author concluded that the waved virgin human hair treated with TG adjusted to pH 9.0 with ammonia solution was less damaged as compared with the waved hair treated with TGA, despite its good waving efficiency, since not only were the GGG and GGT conformations disconnected, but they were also changed to the TGT conformation by performing the reduction process with TG.

This article is protected by copyright. All rights reserved.



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Disruption of human stratum corneum lipid structure by sodium dodecyl sulfate

Abstract

Objective

Surfactants are major ingredients of body soaps and cleansers. Among them, harsh ones have been demonstrated to damage the skin. Stratum corneum (SC), the outermost barrier of skin layer, is rich in intercellular lipids. This lipid structure can be disrupted by surfactants, impairing the barrier function of the skin. Thus, we investigated the surfactant-induced disruption of the intercellular lipid structure of human SC at the molecular level using synchrotron X-ray diffraction.

Methods

SC samples from the breast of female Caucasians were treated with sodium dodecyl sulfate (SDS) and analyzed by small-angle and wide-angle X-ray diffraction.

Results

We found that an aqueous SDS solution affected the long lamellar structure, which became disorganized. The final disordered lipid state was reached through two or more types of structural change. We propose that the disordered lipid state results from incorporation of SDS into the long lamellar structure. In contrast, the lattice constants in the short lamellar and the hydrocarbon-chain packing structures remained almost unchanged after SDS treatment.

Conclusion

We conclude that the disruption of the long lamellar structure plays a key role in the damage to the SC caused by detergents. To our knowledge, this is the first report to clarify the details of the disorganization of the intercellular lipid structure upon surfactant application. The knowledge obtained herein may allow the development of skin restoration methods and cleanser products that do not affect skin barrier functions.

This article is protected by copyright. All rights reserved.



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Morphology-dependent sensing performance of dihydro-tetrazine functionalized MOF toward Al(III)

Publication date: March 2018
Source:Ultrasonics Sonochemistry, Volume 41
Author(s): Sayed Ali Akbar Razavi, Mohammad Yaser Masoomi, Ali Morsali
A pillared MOF, [Zn(OBA)(H2DPT)0.5].DMF (TMU-34), based on dihydro tetrazine functionalized pillar spacer (H2DPT=3,6-di(pyridin-4-yl)-1,4-dihydro-1,2,4,5-tetrazine) and V-shape dicarboxylate linker (H2OBA=4,4′-oxybis(benzoic acid)) was synthesized by reflux and ultrasonic methods. The effects of sonication time, initial concentration of reagents and sonication power on size and morphology have been optimized. This MOF has been characterized by scanning electron microscopy, FT-IR spectra, X-ray powder diffraction and N2 adsorption at 77K. Bulk and nano samples of TMU-34 have been applied in cation sensing for detection of Al(III) in presence of other cations (Na(I), Mg(II), Sr(II), Al(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Pb(II), Hg(II),Cr(III), Li(I), Fe(III), K(I)). The results show that nano powder of TMU-34 with uniform separated plate-like morphology (TMU-34-F) has higher detection limit and short response time compared to bulk material. So, in this work we show the application of luminescent metal-organic frameworks synthesized by sonochemistry approach in effective cation detection.



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Impact of N-methylation of the substance P 1–7 amide on anti-allodynic effect in mice after peripheral administration

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Anna Skogh, Anna Lesniak, Fabienne Z. Gaugaz, Richard Svensson, Gunnar Lindeberg, Rebecca Fransson, Fred Nyberg, Mathias Hallberg, Anja Sandström
Substance P 1–7 (SP1–7, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic degradation of the tachykinin substance P (SP). This heptapeptide often opposes the effects of the mother peptide. Hence, SP1–7 is having anti-inflammatory, anti-nociceptive and anti-hyperalgesic effects in experimental models. Despite all encouraging properties of SP1–7 its exact mode of action has not yet been elucidated which has hampered further development of this heptapeptide in drug discovery. Contrary to SP that mediates its biological activity via the NK-1 receptor, the N-terminal fragment SP1–7 acts through an unknown target that is distinct from all known opioid and tachykinin receptors. The SP1–7 amide 1 (Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) was previously shown to be superior to the endogenous SP1–7 in all experimental pain models where the two compounds were compared. Herein, we report that N-methylation scan of the backbone of the SP1–7 amide (1) results in peptides that are significantly less prone to undergo proteolysis in plasma from both mouse and human. However, with the two exceptions of the [MeLys3]SP1–7 amide (3) and the [MeGln5]SP1–7 amide (4), the peptides with a methyl group attached to the backbone are devoid of significant anti-allodynic effects after peripheral administration in the spared nerve injury (SNI) mouse model of neuropathic pain. It is suggested that the N-methylation does not allow these peptides to form the accurate bioactive conformations or interactions required for efficient binding to the macromolecular target. The importance of intact N-terminal Arg1 and C-terminal Phe7, anticipated to serve as address and message residues, respectively, for achieving the anti-allodynic effect is emphasized. Notably, the three heptapeptides: the SP1–7 amide (1), the [MeLys3]SP1–7 amide (3) amide and the [MeGln5]SP1–7 amide (4) are all considerably more effective in the SNI mouse model than gabapentin that is widely used in the clinic for treatment of neuropathic pain.

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Factor analysis in optimization of formulation of high content uniformity tablets containing low dose active substance

Publication date: 15 November 2017
Source:European Journal of Pharmaceutical Sciences, Volume 109
Author(s): Ivana Lukášová, Jan Muselík, Aleš Franc, Roman Goněc, Filip Mika, David Vetchý
Warfarin is intensively discussed drug with narrow therapeutic range. There have been cases of bleeding attributed to varying content or altered quality of the active substance. Factor analysis is useful for finding suitable technological parameters leading to high content uniformity of tablets containing low amount of active substance. The composition of tabletting blend and technological procedure were set with respect to factor analysis of previously published results. The correctness of set parameters was checked by manufacturing and evaluation of tablets containing 1–10mg of warfarin sodium. The robustness of suggested technology was checked by using "worst case scenario" and statistical evaluation of European Pharmacopoeia (EP) content uniformity limits with respect to Bergum division and process capability index (Cpk). To evaluate the quality of active substance and tablets, dissolution method was developed (water; EP apparatus II; 25rpm), allowing for statistical comparison of dissolution profiles. Obtained results prove the suitability of factor analysis to optimize the composition with respect to batches manufactured previously and thus the use of metaanalysis under industrial conditions is feasible.

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Data on farmers' determinants of manure and inorganic fertiliser use in the semi-arid Ethiopian Rift Valley

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Publication date: October 2017
Source:Data in Brief, Volume 14
Author(s): Shiro Mukai
This article contains the data on farmers' determinants of binary choices for manure use (i.e., manure is used or unused) and fertiliser use (i.e., fertiliser is used or unused) at their fields in semi-arid northern Ethiopian Rift Valley. The data includes (i) a schematic diagram that represents local farmers' distinctions of the crop field types in terms of the distance from their houses and soil fertility and (ii) a table that describes a representative farmer's crop sequences and soil fertilisation methods in two consecutive years. Details about the literature review of the previous case studies on farmers' determinants of manure application technique adoption conducted in some parts of sub-Saharan Africa where cattle dung is used for manure are also summarized in a table. A table shows descriptive statistics of the independent variables used in the empirical analyses. Summary statistics of 4 binomial logit models and 4 multinomial logit models are indicated in a table, which represent model fit. Last two tables exhibited in this article show the logit analyses.



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Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer

Abstract

Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer. We studied the effect of MIA602 and MIA690 on thyroid cancer in vitro, using human thyroid cancer cell lines, and in vivo, using chicken embryo chorioallantoic membrane (CAM) assays. We found that mRNA for GHRH and GHRH receptor is expressed in thyroid cell lines and in samples of thyroid tumors. Immunohistochemistry confirmed the expression of GHRHR protein in specimens of thyroid tumor. We observed that GHRH antagonists inhibited the growth and increased apoptosis of thyroid cancer cells. In vivo, the antagonists inhibited growth and angiogenesis of engrafted thyroid tumors. Our results suggest that GHRH expression may play a role in growth of thyroid cancer and that GHRH antagonists can be a therapeutic option for thyroid cancer patients.



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A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN

Abstract

Dowling-Degos disease, featuring reticulate pigmentation, and familial hidradenitis suppurativa share many clinical features including autosomal dominant inheritance, flexural location and follicular defects. The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. Here we report 4 additional families of Jewish Ashkenazi origin who presented with clinical features characteristic of both disorders. All patients were found to carry the same, heterozygous mutation in PSENEN (c.168T>G, p.Y56X). Haplotype analysis revealed that the mutation originated from a common ancestor. Dowling-Degos disease- as well as hidradenitis suppurativa-associated genes have been shown to encode important regulators of Notch signaling. Accordingly, using a reporter assay, we demonstrated decreased Notch activity in patient's keratinocytes. The present data confirm the genetic basis of the combined Dowling-Degos disease-hidradenitis suppurativa phenotype and suggest that Notch signaling may play a central role in the pathogenesis of this rare condition.

This article is protected by copyright. All rights reserved.



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Development: Transcriptomic blueprints

Nature Reviews Genetics. doi:10.1038/nrg.2017.77

Author: Linda Koch



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An Exploratory Clinical Study of Apatinib for the 2nd Treatment of Esophageal Cancer or Esophageal and Gastric

Conditions:   Esophagus Cancer, Stage III;   Esophageal Gastric Cardia Type Metaplasia;   Esophagus Cancer, Stage IV
Intervention:   Drug: Apatinib
Sponsor:   Tianjin Medical University Cancer Institute and Hospital
Recruiting - verified July 2017

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Stereotactic Radiotherapy of the Resection Cavity of Brain Metastases vs. Post-operative Whole-brain Radiotherapy

Condition:   Brain Metastases, Adult
Interventions:   Radiation: post-operative stereotactic radiosurgery (SRS);   Radiation: Whole brain radiotherapy (WBRT)
Sponsors:   Juergen Debus;   Heidelberg University
Not yet recruiting - verified September 2017

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Optogenetic Inhibition of Medial Prefrontal Cortex–Pontine Nuclei Projections During the Stimulus-free Trace Interval Impairs Temporal Associative Motor Learning

Abstract
The medial prefrontal cortex (mPFC) is closely involved in many higher-order cognitive functions, including learning to associate temporally discontiguous events (called temporal associative learning). However, direct evidence for the role of mPFC and the neural pathway underlying modulation of temporal associative motor learning is sparse. Here, we show that optogenetic inhibition of the mPFC or its axon terminals at the pontine nuclei (PN) during trace intervals or whole trial period significantly impaired the trace eyeblink conditioning (TEC), but had no significant effects on TEC during the conditioned stimulus or intertrial interval period. Our results suggest that activities associated with the mPFC–PN projection during trace intervals is crucial for trace associative motor learning. This finding is of great importance in understanding the mechanisms and the relevant neural pathways underlying mPFC modulation of temporal associative motor learning.

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Comprehensive Morpho-Electrotonic Analysis Shows 2 Distinct Classes of L2 and L3 Pyramidal Neurons in Human Temporal Cortex

Abstract
There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as "slim-tufted" and "profuse-tufted" HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs.

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