NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Purpose: The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [18F]fluoromisonidazole ([18F]FMISO). Methods: [18F]FMISO PET imaging was performed with the dedicated small-animal PET scanner NanoPET (Oxford Positron Systems) and ten different human tumour xenografts in nude mice as well as B16 melanoma tumours in syngeneic Balb/c mice. For comparison, [18F]fluorodeoxyglucose ([18F]FDG) PET scans were also performed in the mice bearing human tumour xenografts. Results: In 10 out of 11 experimental tumour models, [18F]FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter- and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR75% and TMRR5 (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [18F]FMISO uptake in the tumours. The variability observed in [18F]FMISO uptake was related neither to tumour size nor to the injected mass of the radiotracer. The pattern of normoxic and hypoxic regions within the human tumour xenografts, however, correlated with glucose metabolism as revealed by comparison of [18F]FDG and [18F]FMISO images. Conclusion: This study demonstrates the feasibility and utility of [18F]FMISO for imaging murine tumour models using NanoPE

18F-choline in experimental soft tissue infection assessed with autoradiography and high-resolution PET

For each oncological tracer it is important to know the uptake in non-tumorous lesions. The purpose of this study was to measure the accumulation of fluorine-18 choline (FCH), a promising agent for the evaluation of certain tumour types, in infectious tissue. Unilateral thigh muscle abscesses were induced in five rats by intramuscular injection of 0.1ml of a bacterial suspension (Staphylococcus aureus, 1.2×109CFU/ml). In all animals, FCH accumulation was measured with high-resolution positron emission tomography (PET) on day 6. Autoradiography of the abscess and ipsilateral healthy muscle was performed on day 7 (three animals) and day 11 (two animals) and correlated with histology. In addition, 18F-fluorodeoxyglucose (FDG) PET was performed on day 5. Increased FCH uptake was noted in specific layers of the abscess wall which contained an infiltrate of mainly granulocytes on day 7 and mainly macrophages on day 11. The autoradiographic standardised uptake values in the most active part of the abscess wall were 2.99 on day 7 (n=3) and 4.05 on day 11 (n=2). In healthy muscle the corresponding values were 0.99 and 0.64. The abscesses were clearly visualised on the FCH and FDG PET images. In conclusion, this study demonstrated avid FCH accumulation in inflammatory tissue, which limits the specificity of FCH for tumour detection. Future studies are now needed to determine the degree of this limitation in human cancer patient

Deliberation and Identity Rules : The Effect of Anonymity, Pseudonyms and Real-Name Requirements on the Cognitive Complexity of Online News Comments

How do identity rules influence online deliberation? We address this question by drawing on a data set of 45 million comments on news articles on the Huffington Post from January 2013 to May 2015. At the beginning of this period, the site allowed commenting under what we call non-durable pseudonyms. In December 2013, Huffington Post moved to regulate its forum by requiring users to authenticate their accounts. And in June 2014, Huffington Post outsourced commenting to Facebook altogether, approximating a ‘real-name’ environment. We find a significant increase in the cognitive complexity of comments (a proxy for one aspect of deliberative quality) during the middle phase, followed by a decrease following the shift to real-name commenting through Facebook. Our findings challenge the terms of the apparently simple trade-off between the goods and bads of anonymous and real-name environments and point to the potential value of durable pseudonymity in the context of online discussion

Evaluation of pulse rate measurement with a wrist worn device during different tasks and physical activity

The purpose of this study was to evaluate the wrist-worn device Mio FUSE, which estimates heart rate (HR) based on photo-plethysmography, 1) in a large study group during a standardised activity, 2) in a small group during a variety of activities and 3) to investigate factors affecting HR accuracy in a real-world setting. First, 53 male participants (20 ±1 years; 1.79 ±0.07 m; 76.1 ±10.5 kg) completed a 35-km march wearing the Equivital EQ-02 as a criterion measure. Second, 5 participants (whereof 3 female; 29 ±5 years; 1.74 ±0.07 m; 67.8 ±11.1 kg) independently performed 25 activities, categorised as sitting passive, sitting active, standing, cyclic and anti-cyclic activities with the Polar H7 as a criterion device. Equivalence testing and Bland-and-Altman analyses were undertaken to assess the accuracy to the criterion devices. Third, confounders affecting HR accuracy were investigated using multiple backwards regression analyses. The Mio FUSE was equivalent to the respective criterion measures with only small systematic biases of -3.5 bpm (-2.6%) and -1.7 bpm (-1.3%) with limits of agreements of ±10.1 bpm and ±10.8 bpm during the 35-km march and during different activities, respectively. Confounding factors negatively affecting the accuracy of the Mio FUSE were found to include larger wrist size and intensified arm and/or wrist movement. The wrist-worn Mio FUSE can be recommended to estimate overall HR accurately for different types of activities in healthy adults. However, during sporting activities involving intensified arm and/or wrist movement or for detailed continuous analysis, a chest strap is preferred to the Mio FUSE to optimise HR estimation accuracy

Validation of ambulatory monitoring devices to measure energy expenditure and heart rate in a military setting

Objectives.; To investigate the validity of different devices and algorithms used in military organizations worldwide to assess physical activity energy expenditure (PAEE) and heart rate (HR) among soldiers.; Design.; Device validation study.; Methods; . Twenty-three male participants serving their mandatory military service accomplished, firstly, nine different military specific activities indoors, and secondly, a normal military routine outdoors. Participants wore simultaneously an ActiHeart, Everion, MetaMax 3B, Garmin Fenix 3, Hidalgo EQ02, and PADIS 2.0 system. The PAEE and HR data of each system were compared to the criterion measures MetaMax 3B and Hidalgo EQ02, respectively.; Results; . Overall, the recorded systematic errors in PAEE estimation ranged from 0.1 (±1.8) kcal.min; -1; to -1.7 (±1.8) kcal.min; -1; for the systems PADIS 2.0 and Hidalgo EQ02 running the Royal Dutch Army algorithm, respectively, and in the HR assessment ranged from -0.1 (±2.1) b.min; -1; to 0.8 (±3.0) b.min; -1; for the PADIS 2.0 and ActiHeart systems, respectively. The mean absolute percentage error (MAPE) in PAEE estimation ranged from 29.9% to 75.1%, with only the Everion system showing an overall MAP

Prediction of human core body temperature using non-invasive measurement methods

The measurement of core body temperature is an efficient method for monitoring heat stress amongst workers in hot conditions. However, invasive measurement of core body temperature (e.g. rectal, intestinal, oesophageal temperature) is impractical for such applications. Therefore, the aim of this study was to define relevant non-invasive measures to predict core body temperature under various conditions. We conducted two human subject studies with different experimental protocols, different environmental temperatures (10°C, 30°C) and different subjects. In both studies the same non-invasive measurement methods (skin temperature, skin heat flux, heart rate) were applied. A principle component analysis was conducted to extract independent factors, which were then used in a linear regression model. We identified six parameters (three skin temperatures, two skin heat fluxes and heart rate), which were included for the calculation of two factors. The predictive value of these factors for core body temperature was evaluated by a multiple regression analysis. The calculated root mean square deviation (rmsd) was in the range from 0.28°C to 0.34°C for all environmental conditions. These errors are similar to previous models using non-invasive measures to predict core body temperature. The results from this study illustrate that multiple physiological parameters (e.g. skin temperature and skin heat fluxes) are needed to predict core body temperature. In addition, the physiological measurements chosen in this study and the algorithm defined in this work are potentially applicable as real-time core body temperature monitoring to assess health risk in broad range of working conditions

Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies

INTRODUCTION: We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes. METHODS: A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD. RESULTS: Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%. CONCLUSION: DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD

Abrupt reversal in emissions and atmospheric abundance of HCFC-133a (CF3CH2Cl)

Hydrochlorofluorocarbon HCFC-133a (CF3CH2Cl) is an anthropogenic compound whose consumption for emissive use is restricted under the Montreal Protocol. A recent study showed rapidly increasing atmospheric abundances and emissions. We report that, following this rise, the at- mospheric abundance and emissions have declined sharply in the past three years. We find a Northern Hemisphere HCFC-133a increase from 0.13 ppt (dry air mole fraction in parts-per-trillion) in 2000 to 0.50 ppt in 2012–mid-2013 followed by an abrupt reversal to 0.44 ppt by early 2015. Global emissions derived from these observations peaked at 3.1 kt in 2011, followed by a rapid decline of 0.5 kt yr−2 to 1.5 kt yr−1 in 2014. Sporadic HCFC-133a pollution events are detected in Europe from our high-resolution HCFC-133a records at three European stations, and in Asia from sam- ples collected in Taiwan. European emissions are estimated to be <0.1 kt yr−1 although emission hotspots were identi- fied in France

Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep.

In this study, we determined the effect of maternal undernutrition in the periconceptional (PCUN: ~80 days before to 6 days after conception) and preimplantation (PIUN: 0-6 days after conception) periods on the mRNA and protein abundance of key factors regulating myogenesis and protein synthesis, and on the relationship between the abundance of these factors and specific microRNA expression in the quadriceps muscle of singleton and twin fetal sheep at 135-138 days of gestation. PCUN and PIUN resulted in a decrease in the protein abundance of MYF5, a factor which determines the myogenic lineage, in singletons and twins. Interestingly, there was a concomitant increase in insulin-like growth factor-1 mRNA expression, a decrease in the protein abundance of the myogenic inhibitor, myostatin (MSTN), and an increase in the mRNA and protein abundance of the MSTN inhibitor, follistatin (FST), in the PCUN and PIUN groups in both singletons and twins. These promyogenic changes may compensate for the decrease in MYF5 protein abundance evoked by early embryonic undernutrition. PCUN and PIUN also increased the protein abundance of phosphorylated eukaryotic translation initiation factor binding protein 1 (EIF4EBP1; T70 and S65) in fetal muscle in singletons and twins. There was a significant inverse relationship between the expression of miR-30a-5p, miR-30d-5p, miR-27b-3p, miR106b-5p, and miR-376b and the protein abundance of mechanistic target of rapamycin (MTOR), FST, or MYF5 in singletons or twins. In particular, the expression of miR-30a-5p was increased and MYF5 protein abundance was decreased, in PCUN and PIUN twins supporting the conclusion that the impact of PCUN and PIUN is predominantly on the embryo