The MEG/EEG inverse problem is ill-posed, giving different source reconstructions depending on the initial assumption sets. Parametric Empirical Bayes allows one to implement most popular MEG/EEG ...inversion schemes (Minimum Norm, LORETA, etc.) within the same generic Bayesian framework. It also provides a cost-function in terms of the variational Free energy—an approximation to the marginal likelihood or evidence of the solution. In this manuscript, we revisit the algorithm for MEG/EEG source reconstruction with a view to providing a didactic and practical guide. The aim is to promote and help standardise the development and consolidation of other schemes within the same framework. We describe the implementation in the Statistical Parametric Mapping (SPM) software package, carefully explaining each of its stages with the help of a simple simulated data example. We focus on the Multiple Sparse Priors (MSP) model, which we compare with the well-known Minimum Norm and LORETA models, using the negative variational Free energy for model comparison. The manuscript is accompanied by Matlab scripts to allow the reader to test and explore the underlying algorithm.
•We revisit the Bayesian source inversion algorithm for M/EEG source reconstruction.•We provide a didactic and practical guide with software examples.•The aim is to help standardize the development of other schemes.
The authors performed a cross-sectional analysis to evaluate the association between arsenic exposure from drinking water and blood pressure using baseline data of 10,910 participants in the Health ...Effects of Arsenic Longitudinal Study in Bangladesh (October 2000–May 2002). A time-weighted well arsenic concentration (TWA) based on current and past use of drinking wells was derived. Odds ratios for high pulse pressure (≥55 mmHg) by increasing TWA quintiles (≤8, 8.1–40.8, 40.9–91.0, 91.1–176.0, and 176.1–864.0 μg/liter) were 1.00 (referent), 1.39 (95% confidence interval (CI): 1.14, 1.71), 1.21 (95% CI: 0.99, 1.49), 1.19 (95% CI: 0.97, 1.45), and 1.19 (95% CI: 0.97, 1.46). Among participants with a lower than average dietary intake level of B vitamins and folate, the odds ratios for high pulse pressure by increasing TWA quintiles were 1.00 (referent), 1.84 (95% CI: 1.07, 3.16), 1.89 (95% CI: 1.11, 3.20), 1.83 (95% CI: 1.09, 3.07), and 1.89 (95% CI: 1.12, 3.20). The odds ratios for systolic hypertension suggest a similar but weaker association. No apparent associations were observed between TWA and general or diastolic hypertension. These findings indicate that the effect of low-level arsenic exposure on blood pressure is nonlinear and may be more pronounced in persons with lower intake of nutrients related to arsenic metabolism and cardiovascular health. Future research is needed to evaluate the effect of low-level arsenic exposure on specific cardiovascular outcomes.
This article discusses dependencies to calculate the vertical drain wells taking into account evaporation inversion. In a zone near the well,where the depth of groundwater level (GWL) is below a ...critical level, the inversion is set as a constant value. In a zone,where GWL is above a critical level, evaporation inversion is linearly dependent on GWL depth which is unknown in advance. Flowing from underlying aquifers has been taken into account. To illustrate the importance of detailed accounting of evaporation inversion in Central Asian climatic conditions, the forecasted recessions of GWL were compared to those calculated using conventional methods. Calculations were made for climatic and hydrogeological conditions of the northern part of Bishkek.
Hydrogen has been inferred to occur in enhanced concentrations within permanently shadowed regions and, hence, the coldest areas of the lunar poles. The Lunar Crater Observation and Sensing Satellite ...(LCROSS) mission was designed to detect hydrogen-bearing volatiles directly. Neutron flux measurements of the Moon's south polar region from the Lunar Exploration Neutron Detector (LEND) on the Lunar Reconnaissance Orbiter (LRO) spacecraft were used to select the optimal impact site for LCROSS. LEND data show several regions where the epithermal neutron flux from the surface is suppressed, which is indicative of enhanced hydrogen content. These regions are not spatially coincident with permanently shadowed regions of the Moon. The LCROSS impact site inside the Cabeus crater demonstrates the highest hydrogen concentration in the lunar south polar region, corresponding to an estimated content of 0.5 to 4.0% water ice by weight, depending on the thickness of any overlying dry regolith layer. The distribution of hydrogen across the region is consistent with buried water ice from cometary impacts, hydrogen implantation from the solar wind, and/or other as yet unknown sources.
•LEND/LRO instrument neutron counting data sets have been analyzed to create high resolution maps of epithermal neutron flux at polar regions of the Moon.•The conversion from epithermal neutron flux ...to the H/H2O abundances is presented based on the simple subsurface models.•The polar lunar maps (poleward 70S/70N) of homogeneous hydrogen distribution are derived and discussed.
We present a method of conversion of the lunar neutron counting rate measured by the Lunar Reconnaissance Orbiter (LRO) Lunar Exploration Neutron Detector (LEND) instrument collimated neutron detectors, to water equivalent hydrogen (WEH) in the top ∼1m layer of lunar regolith. Polar maps of the Moon's inferred hydrogen abundance are presented and discussed.
The impacts of climate extremes on terrestrial ecosystems are poorly understood but important for predicting carbon cycle feedbacks to climate change. Coupled climate–carbon cycle models typically ...assume that vegetation recovery from extreme drought is immediate and complete, which conflicts with the understanding of basic plant physiology. We examined the recovery of stem growth in trees after severe drought at 1338 forest sites across the globe, comprising 49,339 site-years, and compared the results with simulated recovery in climate-vegetation models. We found pervasive and substantial "legacy effects" of reduced growth and incomplete recovery for 1 to 4 years after severe drought. Legacy effects were most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins. In contrast, limited or no legacy effects after drought were simulated by current climate-vegetation models. Our results highlight hysteresis in ecosystem-level carbon cycling and delayed recovery from climate extremes.
,
, and other members of the Enterobacteriaceae family are common human pathogens that have acquired broad antibiotic resistance, rendering infection by some strains virtually untreatable. ...Enterobacteriaceae are intestinal residents, but generally represent <1% of the adult colonic microbiota. Antibiotic-mediated destruction of the microbiota enables Enterobacteriaceae to expand to high densities in the colon, markedly increasing the risk of bloodstream invasion, sepsis, and death. Here, we demonstrate that an antibiotic-naive microbiota suppresses growth of antibiotic-resistant clinical isolates of
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by acidifying the proximal colon and triggering short chain fatty acid (SCFA)-mediated intracellular acidification. High concentrations of SCFAs and the acidic environment counter the competitive edge that O
and NO
respiration confer upon Enterobacteriaceae during expansion. Reestablishment of a microbiota that produces SCFAs enhances clearance of
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from the intestinal lumen and represents a potential therapeutic approach to enhance clearance of antibiotic-resistant pathogens.
A groundwater residence time study of the deep fluvioglacial aquifer supplying Bishkek, capital of Kyrgyzstan, has found evidence of deep infiltration of recent recharge both in the main periurban ...wellfield and below the city. Commonly-employed hydrochemical markers detected urban influence in the city-centre to depths of 65-100m, but gave no indication of the important role of induced river/canal bed leakage, either upgradient in the periurban wellfield or within the city. This was revealed by O and H stable isotope measurements, which showed that local rainfall/snowfall play little part in the aquifer water balance. More remarkably, the universal detection of CFCs and SF sub(6), including in boreholes with 140-220m deep upper screens, demonstrated that induced leakage of water just a few decades old had penetrated much deeper into the aquifer system than other hydrochemical markers indicated. A two-dimensional flow model set up to test whether such deep pumping-induced leakage could occur below the periurban wellfield confirmed its feasibility. The results imply vertical infiltration rates of 5-10m/year and demonstrate that in this not-uncommon intergranular aquifer setting, deep boreholes with deep screen settings do not necessarily abstract old water. Hence, there are major implications for urban groundwater management and protection in such settings.Original Abstract: L'analyse du temps de residence des eaux souterraines dans un aquifere fluvial profond, d'origine glaciaire, qui alimente en eau Bishek, la capitale de Kyrgyzstan a mis en evidence une recharge recente tant dans le captage en eau que sous la ville meme. Les traceurs chimiques ont indique l'influence urbaine dans le centre de la ville, a une profondeur de 65-100m, mais ils n'ont pas mis en evidence le role important de l'alimentation induite par la couche du fleuve, tant en amont, dans le captage que en aval, dans la ville. Ces effets ont ete releves par des isotopes stables, comme O et h qui ont montre l'influence recente des precipitations dans le bilan hydrique de l'aquifere. De plus, la detection universelle de CFC et de SF6, y compris dans les forages ayant une profondeur de 140-220m, montre que l'alimentation en eau induite de plusieurs decennies a penetre a des profondeurs plus grandes que celles indiques par des traceurs chimiques. Les possibilites d'une drainance verticale induite par les pompages dans le puits profonds du captage ont ete verifiees par un modele bidimensionnel d'ecoulement. Les resultats de la modelisation ont conduit a une infiltration verticale de 5-10m/an et ont demontre aussi que l'eau extraite par des puits profonds dans un aquifere granulaire n'est pas necessairement d'age ancienne. Il s'agit donc des implications majeures concernant la gestion et la protection des captages urbaines en eaux souterraines
Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, ...in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability.
Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1–28 or 1–56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1–28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea.
Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0–2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold.
Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period.
NCT02400476.
•CONTROL trial investigated antidiarrheal strategies including dose escalation in neratinib-treated patients with early HER2+ breast cancer.•Preemptive prophylaxis and dose escalation reduced the rate, severity, and duration of grade 3 diarrhea compared with ExteNET.•Lower diarrhea-related discontinuations and dose reductions in multiple cohorts compared with ExteNET suggested improved tolerability.•Neratinib dose escalation is a particularly promising strategy as it eliminates mandatory prophylaxis and related side-effects.
The presence of hydrated phases in the soil and near‐surface bedrock of Gale Crater is thought to be direct evidence for water‐rock interaction in the crater in the ancient past. Layered sediments ...over the Gale Crater floor are thought to have formed in past epochs due to sediment transport, accumulation, and cementation through interaction with fluids, and the observed strata of water‐bearing minerals record the history of these episodes. The first data analysis of the Dynamic Albedo of Neutrons (DAN) investigation on board the Curiosity rover is presented for 154 individual points of active mode measurements along 1900 m of the traverse over the first 361 Martian solar days in Gale crater. It is found that a model of constant water content within subsurface should be rejected for practically all tested points, whereas a two‐layer model with different water contents in each layer is supported by the data. A so‐called direct two‐layer model (water content increasing with depth) yields acceptable fits for odometry ranges between 0 and 455 m and beyond 638 m. The mean water (H2O) abundances of the top and bottom layers vary from 1.5 to 1.7 wt % and from 2.2 to 3.3 wt %, respectively, while at some tested spots the water content is estimated to be as high as ~5 wt %. The data for odometry range 455–638 m support an inverse two‐layer model (water content decreasing with depth), with an estimated mean water abundance of 2.1 ± 0.1 wt % and 1.4 ± 0.04 wt % in the top and bottom layers, respectively.
Key Points
First analysis of active neutron data from DAN instrument on board MSL roverEstimations of water distribution along MSL rover traverse by DAN instrumentEstimations of chlorine abundance along MSL rover traverse by DAN instrument
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