Before acquiring highest-resolution data of Ceres, questions remained about the emplacement mechanism and source of Occator crater’s bright faculae. Here we report that brine effusion emplaced the ...faculae in a brine-limited, impact-induced hydrothermal system. Impact-derived fracturing enabled brines to reach the surface. The central faculae, Cerealia and Pasola Facula, postdate the central pit, and were primarily sourced from an impact-induced melt chamber, with some contribution from a deeper, pre-existing brine reservoir. Vinalia Faculae, in the crater floor, were sourced from the laterally extensive deep reservoir only. Vinalia Faculae are comparatively thinner and display greater ballistic emplacement than the central faculae because the deep reservoir brines took a longer path to the surface and contained more gas than the shallower impact-induced melt chamber brines. Impact-derived fractures providing conduits, and mixing of impact-induced melt with deeper endogenic brines, could also allow oceanic material to reach the surfaces of other large icy bodies.
Effects of Testosterone Treatment in Older Men Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
The New England journal of medicine,
2016-Feb-18, Letnik:
374, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established.
We assigned 790 men 65 years of age or older with a serum ...testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants.
Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups.
In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.).
Radar‐bright basal reflectors have been detected below the South Polar Layered Deposits (SPLD), using Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) data and have an exciting but ...controversial interpretation: liquid water from subglacial lakes. We mapped the surface of the SPLD immediately above and surrounding the putative lakes (1:2M map scale) in order to provide a geologic context for the interpretation of bright basal reflectors. We use Thermal Emission Imaging System daytime IR (100 m/pixel), Context Camera (6 m/pixel), and High Resolution Imaging Science Experiment (25 cm/pixel) data to characterize geologic units and typical surface roughness. We find evidence for multiple geologic units with features due to CO2 and aeolian‐related processes. We do not find evidence for surface modification linked to postulated lake locations. This is not consistent with the interpretation of the MARSIS basal radar reflector as subglacial lakes.
Plain Language Summary
Radar data are an important tool for understanding what lies below the surface of a geologic feature without having to sample it directly. Returned radar signal strength is higher typically due to a variety of factors, such as a strong difference in material (e.g., rock vs. pure water ice) below the surface. A layer of material below the surface of Mars' south polar permanent ice sheet with unusually high returned radar signal has been detected from orbital data. One interpretation is that this is a subglacial lake, like those on Earth below the Antarctic ice sheet. Here, we use orbital data from two Mars spacecraft to make a map of the surface above the proposed subglacial lake. Our map shows many interesting features but none that would have a clear subglacial lake origin.
Key Points
No geologic unit nor surface feature matches with the location and orientation of the Mars Advanced Radar for Subsurface and Ionosphere Sounding bright reflector “lakes”
Surface textures observed in High Resolution Imaging Science Experiment image data are relatively consistent across mapped geologic units
Surface morphological mapping of the South Polar Layered Deposits subglacial “lakes” region does not provide evidence consistent with the lake hypothesis
This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of ...oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial.
A 2 × 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months.
A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports.
The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.
This study evaluates a direct remote sensing approach from space for the determination of ecosystem photosynthetic light use efficiency (LUE), through measurement of vegetation reflectance changes ...expressed with the Photochemical Reflectance Index (PRI). The PRI is a normalized difference index based on spectral changes at a physiologically active wavelength (~531nm) as compared to a reference waveband, and is only available from a very few satellites. These include the two Moderate-Resolution Imaging Spectroradiometers (MODIS) on the Aqua and Terra satellites each of which have a narrow (10nm) ocean band centered at 531nm. We examined several PRI variations computed with candidate reference bands, since MODIS lacks the traditional 570nm reference band. The PRI computed using MODIS land band 1 (620–670nm) gave the best performance for daily LUE estimation. Through rigorous statistical analyses over a large image collection (n=420), the success of relating in situ daily tower-derived LUE to MODIS observations for northern forests was strongly influenced by satellite viewing geometry. LUE was calculated from CO2 fluxes (molCmol−1 absorbed quanta) measured at instrumented Canadian Carbon Program flux towers in four Canadian forests: a mature fir site in British Columbia, mature aspen and black spruce sites in Saskatchewan, and a mixed deciduous/coniferous forest site in Ontario. All aspects of the viewing geometry had significant effects on the MODIS-PRI, including the view zenith angle (VZA), the view azimuth angle, and the displacement of the view azimuth relative to the solar principal plane, in addition to illumination related variables. Nevertheless, we show that forward scatter sector views (VZA, 16°–45°) provided the strongest relationships to daily LUE, especially those collected in the early afternoon by Aqua (r2=0.83, RMSE=0.003molCmol−1 absorbed quanta). Nadir (VZA, 0°±15°) and backscatter views (VZA, −16° to −45°) had lower performance in estimating LUE (nadir: r2~0.62–0.67; backscatter: r2~0.54–0.59) and similar estimation error (RMSE=0.004–0.005). When directional effects were not considered, only a moderately successful MODIS-PRI vs. LUE relationship (r2=0.34, RMSE=0.007) was obtained in the full dataset (all views & sites, both satellites), but site-specific relationships were able to discriminate between coniferous and deciduous forests. Overall, MODIS-PRI values from Terra (late morning) were higher than those from Aqua (early afternoon), before/after the onset of diurnal stress responses expressed spectrally. Therefore, we identified ninety-two Terra-Aqua “same day” pairs, for which the sum of Terra morning and Aqua afternoon MODIS-PRI values (PRIsum) using all available directional observations was linearly correlated with daily tower LUE (r2=0.622, RMSE=0.013) and independent of site differences or meteorological information. Our study highlights the value of off-nadir directional reflectance observations, and the value of pairing morning and afternoon satellite observations to monitor stress responses that inhibit carbon uptake in Canadian forest ecosystems. In addition, we show that MODIS-PRI values, when derived from either: (i) forward views only, or (ii) Terra/Aqua same day (any view) combined observations, provided more accurate estimates of tower-measured daily LUE than those derived from either nadir or backscatter views or those calculated by the widely used semi-operational MODIS GPP model (MOD17) which is based on a theoretical maximum LUE and environmental data. Consequently, we demonstrate the importance of diurnal as well as off-nadir satellite observations for detecting vegetation physiological processes.
•Photochemical Reflectance Indices (PRI) from MODIS ocean and land bands•PRI evaluated against light use efficiency (LUE) at 4 northern forest sites•MODIS PRI with ocean band 11 and land band 1 gave best performance with daily LUE.•Most accurate LUE from MODIS-PRI used forward views or combined same day Terra/Aqua.•MODIS-PRI provided more accurate estimates of LUE than those calculated by MOD17.
ErbB2/HER2/Neu-overexpressing breast cancers are characterized by poor survival due to high proliferation and metastasis rates and identifying downstream targets of ErbB2 should facilitate developing ...novel therapies for this disease. Gene expression profiling revealed the transcriptional regulator LIM-only protein 4 (LMO4) is upregulated during ErbB2-induced mouse mammary gland tumorigenesis. Although LMO4 is frequently overexpressed in breast cancer and LMO4-overexpressing mice develop mammary epithelial tumors, the mechanisms involved are unknown. In this study, we report that LMO4 is a downstream target of ErbB2 and PI3K in ErbB2-dependent breast cancer cells. Furthermore, LMO4 silencing reduces proliferation of these cells, inducing a G2/M arrest that was associated with decreased cullin-3, an E3-ubiquitin ligase component important for mitosis. Loss of LMO4 subsequently results in reduced Cyclin D1 and Cyclin E. Further supporting a role for LMO4 in modulating proliferation by regulating cullin-3 expression, we found that LMO4 expression oscillates throughout the cell cycle with maximum expression occurring during G2/M and these changes precede oscillations in cullin-3 levels. LMO4 levels are also highest in high-grade/less differentiated breast cancers, which are characteristically highly proliferative. We conclude that LMO4 is a novel cell cycle regulator with a key role in mediating ErbB2-induced proliferation, a hallmark of ErbB2-positive disease.
Mars Reconnaissance Orbiter (MRO), with its arrival in 2006 and nearly continuous operation since, has provided data for the study of martian polar processes spanning nine Mars years. Mars' polar ...deposits have long been thought to preserve records of past climates, potentially readable like terrestrial ice cores. However, unraveling millions of years of history in the ice depends on understanding Mars' current and recent-past climate, including the interactions of atmospheric and surface processes. MRO has allowed for revolutionary discoveries, long-term monitoring of ongoing processes, and multiple complementary datasets to address the question of how the polar ice deposits reflect climatological changes. In part, MRO has been able to do this from its variety of instrumentation simultaneously observing interannual changes in geomorphology of the surface in up to ~25 cm/pixel detail, repeatable processes and changes in the atmosphere, and surface composition, as well as investigating signs of past changes recorded in the icy polar layered deposits. In this paper, we summarize the contribution of MRO to our current understanding of Mars polar science, and in particular how MRO's long-duration mission has improved our understanding of the fundamental volatile cycles on Mars.
•MRO has been making observations of Mars' polar regions across nine Mars years.•MRO's instruments have provided broad information about Mars' polar ice.•Repeat observations by MRO have characterized seasonal and multi-year processes.•Multi-year, −instrument observations are key to understanding Mars' polar processes.
Atmospheric mercury is predominantly present in the gaseous elemental form (Hg0). However, anthropogenic emissions (e.g., incineration, fossil fuel combustion) emit and natural processes create ...particulate-phase mercury (Hg(p)) and divalent reactive gas-phase mercury (RGM). RGM species (e.g., HgCl2, HgBr2) are water-soluble and have much shorter residence times in the atmosphere than Hg0 due to their higher removal rates through wet and dry deposition mechanisms. Manual and automated annular denuder methodologies, to provide high-resolution (1−2 h) ambient RGM measurements, were developed and evaluated. Following collection of RGM onto KCl-coated quartz annular denuders, RGM was thermally decomposed and quantified as Hg0. Laboratory and field evaluations of the denuders found the RGM collection efficiency to be >94% and mean collocated precision to be <15%. Method detection limits for sampling durations ranging from 1 to 12 h were 6.2−0.5 pg m-3, respectively. As part of this research, the authors observed that methods to measure Hg(p) had a significant positive artifact when RGM coexists with Hg(p). This artifact was eliminated if a KCl-coated annular denuder preceded the filter. This new atmospheric mercury speciation methodology has dramatically enhanced our ability to investigate the mechanisms of transformation and deposition of mercury in the atmosphere.
We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC).
Subjects who met the National Institutes of ...Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively.
A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates.
Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive.
In Asia, large-scale studies on anti-HER2 treatment in HER2-positive breast cancer patients with brain metastases are limited. We studied the treatment patterns of these patients in Asia to evaluate ...the impact of anti-HER2 treatment on the time to occurrence of brain metastases (TTBM) and survival after brain metastasis (BM).
A retrospective study of HER2-positive breast cancer patients diagnosed with BM between January 2006 and December 2008 in six Asian countries was conducted. Demographics, tumour characteristics, treatment details, and events dates were collected from medical records.
Data from 280 patients were analysed. Before BM, 63% received anti-HER2 treatment. These patients had significantly longer TTBM than those without anti-HER2 treatment (median 33 vs 19 months; P<0.002). After BM, 93% received radiotherapy, 57% received chemotherapy, and 41% received anti-HER2 treatment (trastuzumab and/or lapatinib). Use of both anti-HER2 agents, primarily sequentially, after BM demonstrated the longest survival after BM and was associated with a significant survival benefit over no anti-HER2 treatment (median 26 vs 6 months; hazard ratio 0.37; 95% CI 0.19-0.72).
Anti-HER2 treatment before BM was associated with longer TTBM. Anti-HER2 treatment after BM was associated with a survival benefit, especially when both trastuzumab and lapatinib were utilised.
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