Virus Identification in Unknown Tropical Febrile Illness Cases Using Deep Sequencing

Dengue virus is an emerging infectious agent that infects an estimated 50–100 million people annually worldwide, yet current diagnostic practices cannot detect an etiologic pathogen in ∼40% of dengue-like illnesses. Metagenomic approaches to pathogen detection, such as viral microarrays and deep sequencing, are promising tools to address emerging and non-diagnosable disease challenges. In this study, we used the Virochip microarray and deep sequencing to characterize the spectrum of viruses present in human sera from 123 Nicaraguan patients presenting with dengue-like symptoms but testing negative for dengue virus. We utilized a barcoding strategy to simultaneously deep sequence multiple serum specimens, generating on average over 1 million reads per sample. We then implemented a stepwise bioinformatic filtering pipeline to remove the majority of human and low-quality sequences to improve the speed and accuracy of subsequent unbiased database searches. By deep sequencing, we were able to detect virus sequence in 37% (45/123) of previously negative cases. These included 13 cases with Human Herpesvirus 6 sequences. Other samples contained sequences with similarity to sequences from viruses in the Herpesviridae, Flaviviridae, Circoviridae, Anelloviridae, Asfarviridae, and Parvoviridae families. In some cases, the putative viral sequences were virtually identical to known viruses, and in others they diverged, suggesting that they may derive from novel viruses. These results demonstrate the utility of unbiased metagenomic approaches in the detection of known and divergent viruses in the study of tropical febrile illness

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Soil water and salinity dynamics under sprinkler irrigated almond exposed to a varied salinity stress at different growth stages

Water use and salinity dynamics in the soils are the crucial management factors influencing the productivity and long-term sustainability of almond and associated environment. In this study, HYDRUS-2D was calibrated and validated on measured spatial and temporal water contents and soil salinities (ECe) distributions under almond irrigated with different water qualities (ECiw) at different physiological stages. During two irrigation seasons (2014–15 and 2015–16), less saline irrigation water (average ECiw 0.78 dS/m) was substituted for recycled irrigation water (average ECiw 1.9 dS/m) in three phenologically different growth stages; pre-pit hardening, kernel growth, and post-harvest, along with no and full substitution during the entire season. Graphical and statistical comparisons (RMSE, MAE, ME, the Nash and Sutcliffe model efficiency, and the coefficient of determination) between measured and simulated values of water contents and ECe in the soil showed a close agreement in all treatments. The water balance data revealed that the seasonal crop evapotranspiration of almond (ETc) varied from 850 to 955 mm in different treatments over the two seasons which represented 68–79% of the water application. Trees irrigated with only less saline water through the two seasons (average ECiw 0.78 dS/m) showed 10% higher plant water uptake as compared to those irrigated with recycled water only (average ECiw 1.9 dS/m). Substituting less saline irrigation during the kernel growth phase, between pit-hardening and harvest, showed greater water uptake by almond and lower salinity buildup in the soil as compared to treatments that substituted less saline irrigation early or late in the season. For all treatments, the average daily root zone ECe (2.4–3.7 dS/m) remained above the level of the almond salinity tolerance threshold (ECe = 1.5 dS/m) throughout the period of investigation. Water use efficiency of almonds varied in a narrow range (0.21–0.25 kg m⁻³) for different treatments. Deep drainage below the root zone (2 m) varied from 22.4–31.1% of the total water application (Rainfall + Irrigation), which was episodic and insufficient to contain the salinity below the almond threshold. This study provided a greater understanding of soil water and salinity dynamics under almond irrigated with waters of varying qualities.V. Phogata, T. Pitt, J.W. Cox, J. Šimůnek, M.A. Skewe

Soil water and salinity dynamics under sprinkler irrigated almond exposed to a varied salinity stress at different growth stages

Water use and salinity dynamics in the soils are the crucial management factors influencing the productivity and long-term sustainability of almond and associated environment. In this study, HYDRUS-2D was calibrated and validated on measured spatial and temporal water contents and soil salinities (ECe) distributions under almond irrigated with different water qualities (ECiw) at different physiological stages. During two irrigation seasons (2014–15 and 2015–16), less saline irrigation water (average ECiw 0.78 dS/m) was substituted for recycled irrigation water (average ECiw 1.9 dS/m) in three phenologically different growth stages; pre-pit hardening, kernel growth, and post-harvest, along with no and full substitution during the entire season. Graphical and statistical comparisons (RMSE, MAE, ME, the Nash and Sutcliffe model efficiency, and the coefficient of determination) between measured and simulated values of water contents and ECe in the soil showed a close agreement in all treatments. The water balance data revealed that the seasonal crop evapotranspiration of almond (ETc) varied from 850 to 955 mm in different treatments over the two seasons which represented 68–79% of the water application. Trees irrigated with only less saline water through the two seasons (average ECiw 0.78 dS/m) showed 10% higher plant water uptake as compared to those irrigated with recycled water only (average ECiw 1.9 dS/m). Substituting less saline irrigation during the kernel growth phase, between pit-hardening and harvest, showed greater water uptake by almond and lower salinity buildup in the soil as compared to treatments that substituted less saline irrigation early or late in the season. For all treatments, the average daily root zone ECe (2.4–3.7 dS/m) remained above the level of the almond salinity tolerance threshold (ECe = 1.5 dS/m) throughout the period of investigation. Water use efficiency of almonds varied in a narrow range (0.21–0.25 kg m−3) for different treatments. Deep drainage below the root zone (2 m) varied from 22.4–31.1% of the total water application (Rainfall + Irrigation), which was episodic and insufficient to contain the salinity below the almond threshold. This study provided a greater understanding of soil water and salinity dynamics under almond irrigated with waters of varying qualities

Quartz solubility in the H2O-NaCl system: a framework for understanding vein formation in porphyry copper deposits

Porphyry copper deposits consist of low-grade stockwork and disseminated sulfide zones that contain characteristic vein generations formed during the evolution of the magmatic-hydrothermal systems. The present contribution proposes an interpretive framework for the formation of porphyry veins that is based on quartz solubility calculations in the H2O-NaCl system at temperatures of 100° to 1,000°C and pressures of 1 to 2,000 bar. The model predicts that high-temperature (500°C) quartz in A veins of deep (4 km) porphyry deposits forms as a result of the cooling of ascending intermediate-density fluids at lithostatic conditions. In deposits of intermediate depths (~1.5–4 km), A vein quartz is mostly formed through cooling of ascending hydrothermal fluids under closed-system conditions or quasi-isobaric cooling under open-system conditions within the two-phase field of the H2O-NaCl system. In shallow (1.5 km) porphyry deposits, rapid decompression can also result in quartz precipitation, forming so-called banded veins. The high-temperature quartz in A veins is associated with potassic alteration. During continued cooling of the magmatic-hydrothermal system, quartz is formed at intermediate temperatures (375°-500°C). This quartz overprints earlier A veins and forms B veins. The fluid inclusion inventory of this quartz generation suggests formation at fluctuating pressure conditions, marking the lithostatic to hydrostatic transition, and the change of wall-rock behavior from ductile to brittle conditions. The quartz is precipitated because of cooling and decompression of the magmatic-hydrothermal fluids under K-feldspar-stable conditions. Textural evidence from many porphyry veins suggests that hypogene sulfide minerals present in A and B veins postdate the quartz, as contacts between quartz and sulfide minerals commonly show dissolution textures. Hypogene sulfide minerals in C veins form at conditions of retrograde quartz solubility, explaining why these veins contain little to no quartz. The quartz solubility calculations suggest that C vein formation occurs at temperatures of ~375° to 450°C from low-salinity, single-phase fluids escaping from the lithostatic to the hydrostatic environment. At the upper end of this temperature range, C veins are biotite stable. However, these veins are associated with chlorite, chlorite-K-feldspar, or chlorite-sericite alteration in most deposits. Late quartz is formed during continued cooling of the hydrothermal fluids at 375°C within the single-phase field of the H2O-NaCl system as quartz solubility under these conditions decreases with temperature. This process is responsible for the formation of quartz in D veins and later base metal-bearing E veins, which are associated with phyllic, advanced argillic, or argillic alteration