Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials?

OBJECTIVES: To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. METHODS: Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. RESULTS: The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 x 10(6) compared with 18.6 x 10(6) for the six normal skin samples (P \u3c 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. CONCLUSIONS: CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease

Analysis and Design of Multiple-Antenna Cognitive Radios with Multiple Primary User Signals

We consider multiple-antenna signal detection of primary user transmission signals by a secondary user receiver in cognitive radio networks. The optimal detector is analyzed for the scenario where the number of primary user signals is no less than the number of receive antennas at the secondary user. We first derive exact expressions for the moments of the generalized likelihood ratio test (GLRT) statistic, yielding approximations for the false alarm and detection probabilities. We then show that the normalized GLRT statistic converges in distribution to a Gaussian random variable when the number of antennas and observations grow large at the same rate. Further, using results from large random matrix theory, we derive expressions to compute the detection probability without explicit knowledge of the channel, and then particularize these expressions for two scenarios of practical interest: 1) a single primary user sending spatially multiplexed signals, and 2) multiple spatially distributed primary users. Our analytical results are finally used to obtain simple design rules for the signal detection threshold.Comment: Revised version (14 pages). Change in titl

Iodine status of young Burkinabe children receiving small-quantity lipid-based nutrient supplements and iodised salt : a cluster-randomised trial

The objective of the present study was to assess the impact of providing small-quantity lipid-based nutrient supplements (SQ-LNS) on the I status of young Burkinabe children. In total, thirty-four communities were assigned to intervention (IC) or non-intervention cohorts (NIC). IC children were randomly assigned to receive 20 g lipid-based nutrient supplements (LNS)/d containing 90 mu g I with 0 or 10 mg Zn from 9 to 18 months of age, and NIC children received no SQ-LNS. All the children were exposed to iodised salt through the national salt iodization programme. Spot urinary iodine (UI), thyroid-stimulating hormone (TSH) and total thyroxine (T-4) in dried blood spots as well as plasma thyroglobulin (Tg) concentrations were assessed at 9 and 18 months of age among 123 IC and fifty-six NIC children. At baseline and at 18 months, UI, TSH and T-4 did not differ between cohorts. Tg concentration was higher in the NIC v. IC at baseline, but this difference did not persist at 18 months of age. In both cohorts combined, the geometric mean of UI was 339.2 (95 % CI 298.6, 385.2) mu g/l, TSH 0.8 (95 % CI 0.7, 0.8) mU/l, T-4 118 (95 % CI 114, 122) nmol/l and Tg 26.0 (95 % CI 24.3, 27.7) mu g/l at 18 months of age. None of the children had elevated TSH at 18 months of age. Marginally more children in NIC (8.9 %) had low T-4 (15 ppm). A reduction of SQ-LNS I content could be considered in settings with similarly successful salt iodisation programmes

Acoustic power absorption and enhancement generated by slow and fast MHD waves

We used long duration, high quality, unresolved (Sun-as-a star) observations collected by the ground based network BiSON and by the instruments GOLF and VIRGO on board the ESA/NASA SOHO satellite to search for solar-cycle-related changes in mode characteristics in velocity and continuum intensity for the frequency range between 2.5mHz < nu < 6.8mHz. Over the ascending phase of solar cycle 23 we found a suppression in the p-mode amplitudes both in the velocity and intensity data between 2.5mHz <nu< 4.5mHz with a maximum suppression for frequencies in the range between 2.5mHz <nu< 3.5mHz. The size of the amplitude suppression is 13+-2 per cent for the velocity and 9+-2 per cent for the intensity observations. Over the range 4.5mHz <nu< 5.5mHz the findings hint within the errors to a null change both in the velocity and intensity amplitudes. At still higher frequencies, in the so called High-frequency Interference Peaks (HIPs) between 5.8mHz <nu < 6.8mHz, we found an enhancement in the velocity amplitudes with the maximum 36+-7 per cent occurring for 6.3mHz <nu< 6.8mHz. However, in intensity observations we found a rather smaller enhancement of about 5+-2 per cent in the same interval. There is evidence that the frequency dependence of solar-cycle velocity amplitude changes is consistent with the theory behind the mode conversion of acoustic waves in a non-vertical magnetic field, but there are some problems with the intensity data, which may be due to the height in the solar atmosphere at which the VIRGO data are taken.Comment: Accepted for publication in A&A. 10 pages, 9 figures

Utilizing Colored Dissolved Organic Matter to Derive Dissolved Black Carbon Export by Arctic Rivers

Wildfires have produced black carbon (BC) since land plants emerged. Condensed aromatic compounds, a form of BC, have accumulated to become a major component of the soil carbon pool. Condensed aromatics leach from soils into rivers, where they are termed dissolved black carbon (DBC). The transport of DBC by rivers to the sea is a major term in the global carbon and BC cycles. To estimate Arctic river DBC export, 25 samples collected from the six largest Arctic rivers (Kolyma, Lena, Mackenzie, Ob’, Yenisey and Yukon) were analyzed for dissolved organic carbon (DOC), colored dissolved organic matter (CDOM), and DBC. A simple, linear regression between DOC and DBC indicated that DBC accounted for 8.9 ± 0.3% DOC exported by Arctic rivers. To improve upon this estimate, an optical proxy for DBC was developed based upon the linear correlation between DBC concentrations and CDOM light absorption coefficients at 254 nm (a254). Relatively easy to measure a254 values were determined for 410 Arctic river samples between 2004 and 2010. Each of these a254 values was converted to a DBC concentration based upon the linear correlation, providing an extended record of DBC concentration. The extended DBC record was coupled with daily discharge data from the six rivers to estimate riverine DBC loads using the LOADEST modeling program. The six rivers studied cover 53% of the pan-Arctic watershed and exported 1.5 ± 0.1 million tons of DBC per year. Scaling up to the full area of the pan-Arctic watershed, we estimate that Arctic rivers carry 2.8 ± 0.3 million tons of DBC from land to the Arctic Ocean each year. This equates to ~8% of Arctic river DOC export, slightly less than indicated by the simpler DBC vs DOC correlation-based estimate. Riverine discharge is predicted to increase in a warmer Arctic. DBC export was positively correlated with river runoff, suggesting that the export of soil BC to the Arctic Ocean is likely to increase as the Arctic warms

Small-quantity lipid-based nutrient supplements containing different amounts of zinc along with diarrhea and malaria treatment increase iron and vitamin A status and reduce anemia prevalence, but do not affect zinc status in young Burkinabe children : a cluster-randomized trial

Background: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC). Methods: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 mu g of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation. Results: At baseline, 35% of children had low adjusted pZC ( 8.3 mg/L) and 47% had low adjusted RBP (< 0.94 mu mol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 mu mol/L vs. 0.86 mu mol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034). Conclusions: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC