Validation of a prognostic scoring system for locally recurrent nasopharyngeal carcinoma treated by stereotactic radiosurgery

<p>Abstract</p> <p>Background</p> <p>Selection of patients with local failure of nasopharyngeal carcinoma (NPC) for appropriate type of salvage treatment can be difficult due to the lack of data on comparative efficacy of different salvage treatments. The purpose of the present study was to validate a previously published prognostic scoring system for local failures of NPC treated by radiosurgery based on reported results in the literature.</p> <p>Methods</p> <p>A literature search yielded 3 published reports on the use of radiosurgery as salvage treatment of NPC that contained sufficient clinical information for validation of the scoring system. Prognostic scores of 18 patients from these reports were calculated and actuarial survival rates were estimated and compared to the original cohort used to design the prognostic scoring system. The area under the receiver operating characteristic curve was also determined and compared between the current and original patient groups.</p> <p>Results</p> <p>The calculated prognostic scores ranged from 0.32 to 1.21, with 15 patients assigned to the poor prognostic group and 3 to the intermediate prognostic group. The actuarial 3-year survival rates in the intermediate and poor prognostic groups were 67% and 0%, respectively. These results were comparable to the observed 3-year survival rates of 74% and 23% in the intermediate and poor prognostic group in the original reports. The area under the receiver operating characteristic curve for the current patient group was 0.846 which was similar to 0.841 in the original group.</p> <p>Conclusion</p> <p>The previously published prognostic scoring system demonstrated good prediction of treatment outcome after radiosurgery in a small group of NPC patients with poor prognosis. Prospective study to validate the scoring system is currently being carried out in our institution.</p

Theoretical investigation of measuring cerebral blood flow in the adult human head using bolus Indocyanine Green injection and near-infrared spectroscopy

To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates. (c) 2007 Optical Society of America

An integrated particle sampler and lung radiation dosimeter

A lung dosimeter that can record the nonradiological hazard of aerosol particles to the lung as well as the radiological hazard of air borne radionuclides that are attached to aerosol particles has been developed. The dosimeter is capable of recording aerosol particles of diameters from 10-2 μm to 102 μ by electrostatic collection in a specially designed dosimeter body. The aerosol size distribution is recorded on a mylar strip and the activity size distribution of α, β, and γ radiation emitting aerosols recorded on another strip coated with α-Al2O3:C. Both strips can be read by a specially built reader, the output of which can be used to calculate the nonradiological hazard and radiological hazard, respectively, and to give an overall picture of the exposure.published_or_final_versio

Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis

BACKGROUND: Local failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear. METHODS: Records of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (5-10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2-6 fractions by SRM. RESULTS: Local control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%). CONCLUSION: Our study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-irradiation, use of fractionated treatment is preferred.link_to_subscribed_fulltex

The interplay of intrinsic and extrinsic bounded noises in genetic networks

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a genetic network. The influence of intrinsic and extrinsic noises on genetic networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: $(i)$ the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, $(ii)$ a model of enzymatic futile cycle and $(iii)$ a genetic toggle switch. In $(ii)$ and $(iii)$ we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possibile functional role of bounded noises

Effect of dose and duration of reduction in dietary sodium on blood pressure levels: systematic review and meta-analysis of randomised trials.

OBJECTIVE: To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration. DESIGN: Systematic review and meta-analysis following PRISMA guidelines. DATA SOURCES: Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019. INCLUSION CRITERIA: Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion. DATA EXTRACTION AND ANALYSIS: Two of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression. RESULTS: 133 studies with 12 197 participants were included. The mean reductions (reduced sodium v usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days' duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction. CONCLUSIONS: The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019140812

The design and testing of a novel mechanomyogram-driven switch controlled by small eyebrow movements

<p>Abstract</p> <p>Background</p> <p>Individuals with severe physical disabilities and minimal motor behaviour may be unable to use conventional mechanical switches for access. These persons may benefit from access technologies that harness the volitional activity of muscles. In this study, we describe the design and demonstrate the performance of a binary switch controlled by mechanomyogram (MMG) signals recorded from the frontalis muscle during eyebrow movements.</p> <p>Methods</p> <p>Muscle contractions, detected in real-time with a continuous wavelet transform algorithm, were used to control a binary switch for computer access. The automatic selection of scale-specific thresholds reduced the effect of artefact, such as eye blinks and head movement, on the performance of the switch. Switch performance was estimated by cued response-tests performed by eleven participants (one with severe physical disabilities).</p> <p>Results</p> <p>The average sensitivity and specificity of the switch was 99.7 ± 0.4% and 99.9 ± 0.1%, respectively. The algorithm performance was robust against typical participant movement.</p> <p>Conclusions</p> <p>The results suggest that the frontalis muscle is a suitable site for controlling the MMG-driven switch. The high accuracies combined with the minimal requisite effort and training show that MMG is a promising binary control signal. Further investigation of the potential benefits of MMG-control for the target population is warranted.</p

The role of 44-methylgambierone in ciguatera fish poisoning: Acute toxicity, production by marine microalgae and its potential as a biomarker for Gambierdiscus spp.

Ciguatera fish poisoning (CFP) is prevalent around the tropical and sub-tropical latitudes of the world and impacts many Pacific island communities intrinsically linked to the reef system for sustenance and trade. While the genus Gambierdiscus has been linked with CFP, it is commonly found on tropical reef systems in microalgal assemblages with other genera of toxin-producing, epiphytic and/or benthic dinoflagellates - Amphidinium, Coolia, Fukuyoa, Ostreopsis and Prorocentrum. Identifying a biomarker compound that can be used for the early detection of Gambierdiscus blooms, specifically in a mixed microalgal community, is paramount in enabling the development of management and mitigation strategies. Following on from the recent structural elucidation of 44-methylgambierone, its potential to contribute to CFP intoxication events and applicability as a biomarker compound for Gambierdiscus spp. was investigated. The acute toxicity of this secondary metabolite was determined by intraperitoneal injection using mice, which showed it to be of low toxicity, with an LD50 between 20 and 38 mg kg-1. The production of 44-methylgambierone by 252 marine microalgal isolates consisting of 90 species from 32 genera across seven classes, was assessed by liquid chromatography-tandem mass spectrometry. It was discovered that the production of this secondary metabolite was ubiquitous to the eight Gambierdiscus species tested, however not all isolates of G. carpenteri, and some species/isolates of Coolia and Fukuyoa

Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods