ALMA Long Baseline Observations of the Strongly Lensed Submillimeter Galaxy HATLAS J090311.6+003906 at z=3.042

We present initial results of very high resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations of the $z$=3.042 gravitationally lensed galaxy HATLAS J090311.6+003906 (SDP.81). These observations were carried out using a very extended configuration as part of Science Verification for the 2014 ALMA Long Baseline Campaign, with baselines of up to 15 km. We present continuum imaging at 151, 236 and 290 GHz, at unprecedented angular resolutions as fine as 23 milliarcseconds (mas), corresponding to an un-magnified spatial scale of ~180 pc at z=3.042. The ALMA images clearly show two main gravitational arc components of an Einstein ring, with emission tracing a radius of ~1.5". We also present imaging of CO(10-9), CO(8-7), CO(5-4) and H2O line emission. The CO emission, at an angular resolution of ~170 mas, is found to broadly trace the gravitational arc structures but with differing morphologies between the CO transitions and compared to the dust continuum. Our detection of H2O line emission, using only the shortest baselines, provides the most resolved detection to date of thermal H2O emission in an extragalactic source. The ALMA continuum and spectral line fluxes are consistent with previous Plateau de Bure Interferometer and Submillimeter Array observations despite the impressive increase in angular resolution. Finally, we detect weak unresolved continuum emission from a position that is spatially coincident with the center of the lens, with a spectral index that is consistent with emission from the core of the foreground lensing galaxy.Comment: 9 pages, 5 figures and 3 tables, accepted for publication in the Astrophysical Journal Letter

ALMA Observations of Asteroid 3 Juno at 60 Kilometer Resolution

We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum images of the asteroid 3 Juno obtained with an angular resolution of 0.042 arcseconds (60 km at 1.97 AU). The data were obtained over a single 4.4 hr interval, which covers 60% of the 7.2 hr rotation period, approximately centered on local transit. A sequence of ten consecutive images reveals continuous changes in the asteroid's profile and apparent shape, in good agreement with the sky projection of the three-dimensional model of the Database of Asteroid Models from Inversion Techniques. We measure a geometric mean diameter of 259pm4 km, in good agreement with past estimates from a variety of techniques and wavelengths. Due to the viewing angle and inclination of the rotational pole, the southern hemisphere dominates all of the images. The median peak brightness temperature is 215pm13 K, while the median over the whole surface is 197pm15 K. With the unprecedented resolution of ALMA, we find that the brightness temperature varies across the surface with higher values correlated to the subsolar point and afternoon areas, and lower values beyond the evening terminator. The dominance of the subsolar point is accentuated in the final four images, suggesting a reduction in the thermal inertia of the regolith at the corresponding longitudes, which are possibly correlated to the location of the putative large impact crater. These results demonstrate ALMA's potential to resolve thermal emission from the surface of main belt asteroids, and to measure accurately their position, geometric shape, rotational period, and soil characteristics.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10 AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analogue HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees). We obtain a high-fidelity image of the 1.0 mm spectral index ($\alpha$), which ranges from $\alpha\sim2.0$ in the optically-thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion around a ~1.3 solar mass star, although complicated by absorption at low blue-shifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

Updating the Food-Based Dietary Guidelines for the Spanish Population: The Spanish Society of Community Nutrition (SENC) Proposal

Diet-related risk factors and physical inactivity are among the leading risk factors for disability and are responsible for a large proportion of the burden of chronic non-communicable diseases. Food-based dietary guidelines (FBDGs) are useful tools for nutrition policies and public health strategies to promote healthier eating and physical activity. In this paper, we discuss the process followed in developing the dietary guidelines for the Spanish population by the Spanish Society of Community Nutrition (SENC) and further explain the collaboration with primary healthcare practitioners as presented in the context of the NUTRIMAD 2018 international congress of SENC. From a health in all policies approach, SENC convened a group of experts in nutrition and public health to review the evidence on diet-health, nutrient intake and food consumption in the Spanish population, as well as food preparation, determinants and impact of diet on environmental sustainability. The collaborative group drafted the document and designed the graphic icon, which was then subject to a consultation process, discussion, and qualitative evaluation. Next, a collaborative group was established to plan a dissemination strategy, involving delegates from all the primary healthcare scientific societies in Spain. A product of this collaboration was the release of an attractive, easy-to-understand publication

Gravity-driven Magnetic Field at ∼1000 au Scales in High-mass Star Formation

A full understanding of high-mass star formation requires the study of one of the most elusive components of the energy balance in the interstellar medium: magnetic fields. We report Atacama Large Millimeter/submillimeter Array (ALMA) 1.2 mm, high-resolution (700 au) dust polarization and molecular line observations of the rotating hot molecular core embedded in the high-mass star-forming region IRAS 18089-1732. The dust continuum emission and magnetic field morphology present spiral-like features resembling a whirlpool. The velocity field traced by the H13CO+ (J = 3-2) transition line reveals a complex structure with spiral filaments that are likely infalling and rotating, dragging the field with them. We have modeled the magnetic field and find that the best model corresponds to a weakly magnetized core with a mass-to-magnetic-flux ratio (λ) of 8.38. The modeled magnetic field is dominated by a poloidal component, but with an important contribution from the toroidal component that has a magnitude of 30% of the poloidal component. Using the Davis-Chandrasekhar-Fermi method, we estimate a magnetic field strength of 3.5 mG. At the spatial scales accessible to ALMA, an analysis of the energy balance of the system indicates that gravity overwhelms turbulence, rotation, and the magnetic field. We show that high-mass star formation can occur in weakly magnetized environments, with gravity taking the dominant role.Fil: Sanhueza, Patricio. National Astronomical Observatory Of Japan; JapónFil: Girart, Josep Miquel. Instituto de Estudios Espaciales de Cataluña; EspañaFil: Padovani, Marco. Osservatorio Astrofisico Di Arcetri; ItaliaFil: Galli, Daniele. Osservatorio Astrofisico Di Arcetri; ItaliaFil: Hull, Charles L. H.. Atacama Large Millimeter-submillimeter Array; ChileFil: Zhang, Qizhou. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Cortes, Paulo. National Radio Astronomy Observatory; Estados UnidosFil: Stephens, Ian. Worcester State University; Estados UnidosFil: Fernandez Lopez, Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Jackson, James M.. NASA Ames Research Center; Estados UnidosFil: Frau, Pau. Csic. Instituto de Ciencias del Espacio; EspañaFil: Kock, Patrick M.. Academia Sinica; ChinaFil: Wu, Benjamin. National Astronomical Observatory Of Japan; JapónFil: Zapata, Luis A.. Instituto de Radioastronomía y Astrofísica; MéxicoFil: Olguin, Fernando. National Tsing Hua University; ChinaFil: Lu, Xing. National Astronomical Observatory Of Japan; JapónFil: Silva, Andrea. National Astronomical Observatory Of Japan; JapónFil: Tang, Ya Wen. Academia Sinica; ChinaFil: Sakai, Takeshi. The University Of Electro-communications; JapónFil: Guzmán, Andrés E.. National Astronomical Observatory Of Japan; JapónFil: Tatematsu, Ken'Ichi. National Astronomical Observatory Of Japan; JapónFil: Nakamura, Fumitaka. National Astronomical Observatory Of Japan; JapónFil: Chen, Huei Ru Vivien. National Tsing Hua University; Chin

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms