Search

The past decade has seen significant progress on the direct detection and characterization of young, self-luminous giant planets at wide orbital separations from their host stars. Some of these planets show evidence for disequilibrium processes like transport-induced quenching in their atmospheres; photochemistry may also be important, despite the large orbital distances. These disequilibrium chemical processes can alter the expected composition, spectral behavior, thermal structure, and cooling history of the planets, and can potentially confuse determinations of bulk elemental ratios, which provide important insights into planet-formation mechanisms. Using a thermo/photochemical kinetics and transport model, we investigate the extent to which disequilibrium chemistry affects the composition and spectra of directly imaged giant exoplanets. Results for specific "young Jupiters" such as HR 8799 b and 51 Eri b are presented, as are general trends as a function of planetary effective temperature, surface gravity, incident ultraviolet flux, and strength of deep atmospheric convection. We find that quenching is very important on young Jupiters, leading to CO/CH4 and N2/NH3 ratios much greater than, and H2O mixing ratios a factor of a few less than, chemical-equilibrium predictions. Photochemistry can also be important on such planets, with CO2 and HCN being key photochemical products. Carbon dioxide becomes a major constituent when stratospheric temperatures are low and recycling of water via the H2 + OH reaction becomes kinetically stifled. Young Jupiters with effective temperatures ≲700 K are in a particularly interesting photochemical regime that differs from both transiting hot Jupiters and our own solar-system giant planets.

Rationale: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population.Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy.Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee.Measurements and Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not.Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status. [ABSTRACT FROM AUTHOR]

The ability to stably maintain visual information over brief delays is central to healthy cognitive functioning, as is the ability to differentiate such internal representations from external inputs. One possible way to achieve both is via multiple concurrent mnemonic representations along the visual hierarchy that differ systematically from the representations of perceptual inputs. To test this possibility, we examine orientation representations along the visual hierarchy during perception and working memory. Human participants directly viewed, or held in mind, oriented grating patterns, and the similarity between fMRI activation patterns for different orientations was calculated throughout retinotopic cortex. During direct viewing of grating stimuli, similarity was relatively evenly distributed amongst all orientations, while during working memory the similarity was higher around oblique orientations. We modeled these differences in representational geometry based on the known distribution of orientation information in the natural world: The "veridical" model uses an efficient coding framework to capture hypothesized representations during visual perception. The "categorical" model assumes that different "psychological distances" between orientations result in orientation categorization relative to cardinal axes. During direct perception, the veridical model explained the data well. During working memory, the categorical model gradually gained explanatory power over the veridical model for increasingly anterior retinotopic regions. Thus, directly viewed images are represented veridically, but once visual information is no longer tethered to the sensory world there is a gradual progression to more categorical mnemonic formats along the visual hierarchy., Competing Interests: Conflict of interest: The authors declare no conflict of interest

Perseverance's Mastcam-Z instrument provides high-resolution stereo and multispectral images with a unique combination of spatial resolution, spatial coverage, and wavelength coverage along the rover's traverse in Jezero crater, Mars. Images reveal rocks consistent with an igneous (including volcanic and/or volcaniclastic) and/or impactite origin and limited aqueous alteration, including polygonally fractured rocks with weathered coatings; massive boulder-forming bedrock consisting of mafic silicates, ferric oxides, and/or iron-bearing alteration minerals; and coarsely layered outcrops dominated by olivine. Pyroxene dominates the iron-bearing mineralogy in the fine-grained regolith, while olivine dominates the coarse-grained regolith. Solar and atmospheric imaging observations show significant intra- and intersol variations in dust optical depth and water ice clouds, as well as unique examples of boundary layer vortex action from both natural (dust devil) and Ingenuity helicopter-induced dust lifting. High-resolution stereo imaging also provides geologic context for rover operations, other instrument observations, and sample selection, characterization, and confirmation.

Observations by several cameras on the Perseverance rover showed a 22° scattering halo around the Sun over several hours during northern midsummer (solar longitude 142°). Such a halo has not previously been seen beyond Earth. The halo occurred during the aphelion cloud belt season and the cloudiest time yet observed from the Perseverance site. The halo required crystalline water-ice cloud particles in the form of hexagonal columns large enough for refraction to be significant, at least 11 μm in diameter and length. From a possible 40-50 km altitude, and over the 3.3 hr duration of the halo, particles could have fallen 3-12 km, causing downward transport of water and dust. Halo-forming clouds are likely rare due to the high supersaturation of water that is required but may be more common in northern subtropical regions during northern midsummer., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2022. The Authors.)

Despite the importance of sand and dust to Mars geomorphology, weather, and exploration, the processes that move sand and that raise dust to maintain Mars' ubiquitous dust haze and to produce dust storms have not been well quantified in situ, with missions lacking either the necessary sensors or a sufficiently active aeolian environment. Perseverance rover's novel environmental sensors and Jezero crater's dusty environment remedy this. In Perseverance's first 216 sols, four convective vortices raised dust locally, while, on average, four passed the rover daily, over 25% of which were significantly dusty ("dust devils"). More rarely, dust lifting by nonvortex wind gusts was produced by daytime convection cells advected over the crater by strong regional daytime upslope winds, which also control aeolian surface features. One such event covered 10 times more area than the largest dust devil, suggesting that dust devils and wind gusts could raise equal amounts of dust under nonstorm conditions.

The vertical opacity structure of the martian atmosphere is important for understanding the distribution of ice (water and carbon dioxide) and dust. We present a new data set of extinction opacity profiles from the NOMAD/UVIS spectrometer aboard the ExoMars Trace Gas Orbiter, covering one and a half Mars Years (MY) including the MY 34 Global Dust Storm and several regional dust storms. We discuss specific mesospheric cloud features and compare with existing literature and a Mars Global Climate Model (MGCM) run with data assimilation. Mesospheric opacity features, interpreted to be water ice, were present during the global and regional dust events and correlate with an elevated hygropause in the MGCM, providing evidence that regional dust storms can boost transport of vapor to mesospheric altitudes (with potential implications for atmospheric escape). The season of the dust storms also had an apparent impact on the resulting lifetime of the cloud features, with events earlier in the dusty season correlating with longer-lasting mesospheric cloud layers. Mesospheric opacity features were also present during the dusty season even in the absence of regional dust storms, and interpreted to be water ice based on previous literature. The assimilated MGCM temperature structure agreed well with the UVIS opacities, but the MGCM opacity field struggled to reproduce mesospheric ice features, suggesting a need for further development of water ice parameterizations. The UVIS opacity data set offers opportunities for further research into the vertical aerosol structure of the martian atmosphere, and for validation of how this is represented in numerical models., (© 2022. The Authors.)

Background/aim: The frequency of adverse events (AEs) in clinical trials without control arms is difficult to interpret., Materials and Methods: This is a systematic literature review of AEs reported from the placebo arms of randomized cancer trials in PubMed between 2008 and 2020., Results: We found 80 placebo patient cohorts in 73 publications, describing 17,968 subjects who received placebo. Headaches were reported in 35 patient cohorts with an average frequency of 12.3% (+/- SD=8.0, range=0.4-34.1), and were more common in cohorts with a median age between 45 and 50 years, with higher performance status, and breast cancer (average 29.8% +/- SD=6.1). AEs leading to discontinuation were reported in 5% of cohorts (+/- SD=5.1, range=0-22.7)., Conclusion: Considering covariates allows more accurate interpretation of the observed AE frequencies in cancer trials., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Daily, global wide angle imaging of Mars clouds in MARCI (MARs Color Imager, (Malin et al., 2008)) ultraviolet and visible bands reveals the spatial/seasonal distributions and physical characteristics of perihelion cloud trails (PCT); a class of high altitude (40-50 km), horizontally extended (200-1000 km, trending W to WSW) water ice clouds formed over specific southern low-to-mid latitude (5S-40S), mesoscale (~50 km) locations during the Mars perihelion, southern summer season. PCT were first reported in association with rim regions of Valles Marineris (Clancy et al., 2009). The current study employs MARCI 2007-2011 imaging to sample the broader distributions and properties of PCT; and indicates several distinct locations of peak occurrences, including SW Arsia Mons, elevated regions of Syria, Solis, and Thaumasia Planitia, along Valles Marineris margins, and the NE rim of Hellas Basin. PCT are present over Mars solar longitudes ( L S ) of 210-310°, in late morning to mid afternoon hours (10am-3pm), and are among the brightest and most distinctive clouds exhibited during the perihelion portion of the Mars orbit. Their locations (i.e., eastern margin origins) correspond to strong local elevation gradients, and their timing to peak solar heating conditions (perihelion, subsolar latitudes and midday local times). They occur approximately on a daily basis among all locations identified (i.e., not daily at a single location). Based on cloud surface shadow analyses, PCT form at 40-50 km aeroid altitudes, where water vapor is generally at near-saturation conditions in this perihelion period (e.g. Millour et al., 2014). They exhibited notable absences during periods of planet encircling and regional dust storm activity in 2007 and 2009, respectively, presumably due to reduced water saturation conditions above 35-40 km altitudes associated with increased dust heating over the vertically extended atmosphere (e.g., Neary et al., 2019). PCT exhibit smaller particle sizes (R eff =0.2-0.5 μ m) than typically exhibited in the lower atmosphere, and incorporate significant fractions of available water vapor at these altitudes. PCT ice particles are inferred to form continuously (over ~4 hours) at their PCT eastern origins, associated with localized updrafts, and are entrained in upper level zonal/meridional winds (towards W or WSW with ~50 m/sec speeds at 40-50 km altitudes) to create long, linear cloud trails. PCT cloud formation is apparently forced in the lower atmosphere (≤10-15 km) by strong updrafts associated with distinctive topographic gradients, such as simulated in mesoscale studies (e.g., Tyler and Barnes, 2015) and indicated by the surface-specific PCT locations. These lower scale height updrafts are proposed to generate vertically propagating gravity waves (GW), leading to PCT formation above ~40 km altitudes where water vapor saturation conditions promote vigorous cloud ice formation. Recent mapping of GW amplitudes at ~25 km altitudes, from Mars Climate Sounder 15 μ m radiance variations (Heavens et al., 2020), in fact demonstrates close correspondences to the detailed spatial distributions of observed PCT, relative to other potential factors such as surface albedo and surface elevation (or related boundary layer depths).

Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission's Perseverance rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 μrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 μrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory Curiosity rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover's Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover's traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover's sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions., Competing Interests: Conflicts of interest/Competing interestsThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Working memory (WM) is important to maintain information over short time periods to provide some stability in a constantly changing environment. However, brain activity is inherently dynamic, raising a challenge for maintaining stable mental states. To investigate the relationship between WM stability and neural dynamics, we used electroencephalography to measure the neural response to impulse stimuli during a WM delay. Multivariate pattern analysis revealed representations were both stable and dynamic: there was a clear difference in neural states between time-specific impulse responses, reflecting dynamic changes, yet the coding scheme for memorised orientations was stable. This suggests that a stable subcomponent in WM enables stable maintenance within a dynamic system. A stable coding scheme simplifies readout for WM-guided behaviour, whereas the low-dimensional dynamic component could provide additional temporal information. Despite having a stable subspace, WM is clearly not perfect-memory performance still degrades over time. Indeed, we find that even within the stable coding scheme, memories drift during maintenance. When averaged across trials, such drift contributes to the width of the error distribution., Competing Interests: The authors have declared that no competing interests exist.

It is unclear to what extent sensory processing areas are involved in the maintenance of sensory information in working memory (WM). Previous studies have thus far relied on finding neural activity in the corresponding sensory cortices, neglecting potential activity-silent mechanisms, such as connectivity-dependent encoding. It has recently been found that visual stimulation during visual WM maintenance reveals WM-dependent changes through a bottom-up neural response. Here, we test whether this impulse response is uniquely visual and sensory-specific. Human participants (both sexes) completed visual and auditory WM tasks while electroencephalography was recorded. During the maintenance period, the WM network was perturbed serially with fixed and task-neutral auditory and visual stimuli. We show that a neutral auditory impulse-stimulus presented during the maintenance of a pure tone resulted in a WM-dependent neural response, providing evidence for the auditory counterpart to the visual WM findings reported previously. Interestingly, visual stimulation also resulted in an auditory WM-dependent impulse response, implicating the visual cortex in the maintenance of auditory information, either directly or indirectly, as a pathway to the neural auditory WM representations elsewhere. In contrast, during visual WM maintenance, only the impulse response to visual stimulation was content-specific, suggesting that visual information is maintained in a sensory-specific neural network, separated from auditory processing areas. SIGNIFICANCE STATEMENT Working memory is a crucial component of intelligent, adaptive behavior. Our understanding of the neural mechanisms that support it has recently shifted: rather than being dependent on an unbroken chain of neural activity, working memory may rely on transient changes in neuronal connectivity, which can be maintained efficiently in activity-silent brain states. Previous work using a visual impulse stimulus to perturb the memory network has implicated such silent states in the retention of line orientations in visual working memory. Here, we show that auditory working memory similarly retains auditory information. We also observed a sensory-specific impulse response in visual working memory, while auditory memory responded bimodally to both visual and auditory impulses, possibly reflecting visual dominance of working memory., (Copyright © 2020 the authors.)

Global dust storms on Mars are rare 1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere 3 , primarily owing to solar heating of the dust 3 . In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars 4 . Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes 5,6 , as well as a decrease in the water column at low latitudes 7,8 . Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H 2 O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H 2 O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals 3 . The observed changes in H 2 O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.

Accelerating antiretroviral therapy (ART) administration, improving retention, and achieving viral suppression in low- and middle-income countries must be prioritized. We evaluated trends and disparities in these milestones in a large Latin American cohort. Adults starting ART (ART start ) from 2003 to 2014 at Caribbean, Central, and South America network for HIV epidemiology sites were assessed for care cascade outcomes: CD4 cell count >200 cells/mm 3 at ART start ; retention (≥1 visit at one year after ART start ); viral suppression (≥1 HIV-1 RNA <200 copies/ml at one year after ART start ). Modified Poisson regression provided adjusted prevalence ratios by age, gender, and HIV transmission risk, accounting for site and year of ART start . Proportions achieving ART start and suppression improved over time (p < 0.05). Older age was associated with better retention and viral suppression, but not ART start at CD4 cell count >200 cells/mm 3 . Females and men who have sex with men (MSM) were more likely to have CD4 cell count >200 cells/mm 3 at ART start . Injection drug users (IDUs) were less likely to be retained while MSM were more likely to achieve viral suppression (all p < 0.05). Despite improvements in these outcomes over the course of a decade in this cohort, significant disparities existed, disadvantaging younger patients, men, and IDUs. These gaps indicate continued progress in providing early diagnosis and ART start remain critical.

Background: Inflammatory bowel diseases (IBD) are believed to be driven by dysregulated interactions between the host and the gut microbiota. Our goal is to characterize and infer relationships between mucosal T cells, the host tissue environment, and microbial communities in patients with IBD who will serve as basis for mechanistic studies on human IBD., Methods: We characterized mucosal CD4 T cells using flow cytometry, along with matching mucosal global gene expression and microbial communities data from 35 pinch biopsy samples from patients with IBD. We analyzed these data sets using an integrated framework to identify predictors of inflammatory states and then reproduced some of the putative relationships formed among these predictors by analyzing data from the pediatric RISK cohort., Results: We identified 26 predictors from our combined data set that were effective in distinguishing between regions of the intestine undergoing active inflammation and regions that were normal. Network analysis on these 26 predictors revealed SAA1 as the most connected node linking the abundance of the genus Bacteroides with the production of IL17 and IL22 by CD4 T cells. These SAA1-linked microbial and transcriptome interactions were further reproduced with data from the pediatric IBD RISK cohort., Conclusions: This study identifies expression of SAA1 as an important link between mucosal T cells, microbial communities, and their tissue environment in patients with IBD. A combination of T cell effector function data, gene expression and microbial profiling can distinguish between intestinal inflammatory states in IBD regardless of disease types.

Background: In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings., Methods: This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care., Results: 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial., Conclusions: Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.

Recent theoretical models propose that working memory is mediated by rapid transitions in 'activity-silent' neural states (for example, short-term synaptic plasticity). According to the dynamic coding framework, such hidden state transitions flexibly configure memory networks for memory-guided behavior and dissolve them equally fast to allow forgetting. We developed a perturbation approach to measure mnemonic hidden states in an electroencephalogram. By 'pinging' the brain during maintenance, we show that memory-item-specific information is decodable from the impulse response, even in the absence of attention and lingering delay activity. Moreover, hidden memories are remarkably flexible: an instruction cue that directs people to forget one item is sufficient to wipe the corresponding trace from the hidden state. In contrast, temporarily unattended items remain robustly coded in the hidden state, decoupling attentional focus from cue-directed forgetting. Finally, the strength of hidden-state coding predicts the accuracy of working-memory-guided behavior, including memory precision.

In the perception of target stimuli in rapid serial visual presentations, the process of temporal integration plays an important role when two targets are presented in direct succession (at Lag 1), causing them to be perceived as a singular episodic event. This has been associated with increased reversals of target order report and elevated task performance in classic paradigms. Yet, most current models of temporal attention do not incorporate a mechanism of temporal integration and it is currently an open question whether temporal integration is a factor in attentional processing: It might be an independent process, perhaps little more than a sensory sampling rate parameter, isolated to Lag 1, where it leaves the attentional dynamics otherwise unaffected. In the present study, these boundary conditions were tested. Temporal target integration was observed across sequences of three targets spanning an interval of 240ms. Integration rates furthermore depended strongly on bottom-up attentional filtering, and to a lesser degree on top-down control. The results support the idea that temporal integration is an adaptive process that is part of, or at least interacts with, the attentional system. Implications for current models of temporal attention are discussed., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries., Methods: Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2-7% of persons known to be living with HIV in these countries., Results: Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm(3). Haiti, Mexico, and several states had >85% retention in care; lower (50-74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America., Conclusions: These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.

New research suggests that magnetoencephalography (MEG) contains rich spatial information for decoding neural states. Even small differences in the angle of neighbouring dipoles generate subtle, but statistically separable field patterns. This implies MEG (and electroencephalography: EEG) is ideal for decoding neural states with high-temporal resolution in the human brain., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is often assumed that information in visual working memory (vWM) is maintained via persistent activity. However, recent evidence indicates that information in vWM could be maintained in an effectively "activity-silent" neural state. Silent vWM is consistent with recent cognitive and neural models, but poses an important experimental problem: how can we study these silent states using conventional measures of brain activity? We propose a novel approach that is analogous to echolocation: using a high-contrast visual stimulus, it may be possible to drive brain activity during vWM maintenance and measure the vWM-dependent impulse response. We recorded electroencephalography (EEG) while participants performed a vWM task in which a randomly oriented grating was remembered. Crucially, a high-contrast, task-irrelevant stimulus was shown in the maintenance period in half of the trials. The electrophysiological response from posterior channels was used to decode the orientations of the gratings. While orientations could be decoded during and shortly after stimulus presentation, decoding accuracy dropped back close to baseline in the delay. However, the visual evoked response from the task-irrelevant stimulus resulted in a clear re-emergence in decodability. This result provides important proof-of-concept for a promising and relatively simple approach to decode "activity-silent" vWM content using non-invasive EEG.

Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal immunity is complex and a combination of host genetics and environmental factors play a significant role in regulating intestinal immunity. Due to this complexity, no mouse model to date gives a complete and accurate representation of human intestinal diseases, such as inflammatory bowel diseases. However, intestinal tissue from patients undergoing bowel resection reflects a condition of severe disease that has failed treatment; hence a more dynamic perspective of varying inflammatory states in IBD could be obtained through the analyses of pinch biopsy material. Here we describe our protocol for analyzing mucosal pinch biopsies collected predominantly during colonoscopies. We have optimized flow cytometry panels to analyze up to 8 cytokines produced by CD4+ and CD8+ cells, as well as for characterizing nuclear proteins and transcription factors such as Ki67 and Foxp3. Furthermore, we have optimized approaches to analyze the production of cytokines, including TGF-beta from direct ex vivo cultures of pinch biopsies and LPMCs isolated from biopsies. These approaches are part of our workflow to try and understand the role of the gut microbiota in complex and dynamic human intestinal diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Experiential learning in medical education, as exemplified by objective structured clinical examinations (OSCEs), is a well-validated approach for improving trainee performance. Furthermore, the Accreditation Council for Graduate Medical Education has identified OSCEs as an ideal method for assessing the core competency of interpersonal and communication skills. Here, we describe a novel educational tool, the inflammatory bowel disease OSCE (IBD OSCE), to assess and improve this clinical skill set in Gastroenterology fellows., Methods: We developed a 4-station IBD OSCE that assessed shared decision making, physician-physician communication, and physician-patient consultative skills specifically related to the care of patients with IBD. Each station was videotaped and observed live by faculty gastroenterologists. Behaviorally anchored checklists were scored independently by a faculty observer and the standardized patient/physician, who both provided feedback to the fellow immediately after each case. Post-OSCE, fellows attended a debriefing session on patient communication and were surveyed to assess their perspective on the examination's educational value., Results: Twelve second-year gastroenterology fellows from 5 fellowship programs participated in the IBD OSCE. Fellows performed well in all measured domains and rated the experience highly for its educational value. Fellows cited IBD as an area of relative deficiency in their education compared with other knowledge areas within gastroenterology., Conclusions: To our knowledge, this is the first OSCE designed specifically for the evaluation of skills as they relate to IBD management. Using OSCEs for IBD education provides an opportunity to robustly assess core competencies and the role of the physician as an educator.

In dynamic sensory environments, successive stimuli may be combined perceptually and represented as a single, comprehensive event by means of temporal integration. Such perceptual segmentation across time is intuitively plausible. However, the possible costs and benefits of temporal integration in perception remain underspecified. In the present study pupil dilation was analyzed as a measure of mental effort. Observers viewed either one or two successive targets amidst distractors in rapid serial visual presentation, which they were asked to identify. Pupil dilation was examined dependent on participants' report: dilation associated with the report of a single target, of two targets, and of an integrated percept consisting of the features of both targets. There was a clear distinction between dilation observed for single-target reports and integrations on the one side, and two-target reports on the other. Regardless of report order, two-target reports produced increased pupil dilation, reflecting increased mental effort. The results thus suggested that temporal integration reduces mental effort and may thereby facilitate perceptual processing.

The mucosal microbiota lives in close proximity with the intestinal epithelium and may interact more directly with the host immune system than the luminal/fecal bacteria. The availability of nutrients in the mucus layer of the epithelium is also very different from the gut lumen environment. Inferred metagenomic analysis for microbial function of the mucosal microbiota is possible by PICRUSt. We recently found that by using this approach, actively inflamed tissue of ulcerative colitis (UC) patients have mucosal communities enriched for genes involved in lipid and amino acid metabolism, and reduced for carbohydrate and nucleotide metabolism. Here, we find that the same bacterial taxa (e.g. Acinetobacter) and predicted microbial pathways enriched in actively inflamed colitis tissue are also enriched in the mucosa of subjects undergoing routine screening colonoscopies, when compared with paired samples of luminal/fecal bacteria. These results suggest that the mucosa of healthy individuals may be a reservoir of aerotolerant microbial communities expanded during colitis.

Selective attention and working memory capacity (WMC) are related constructs, but debate about the manner in which they are related remains active. One elegant explanation of variance in WMC is that the efficiency of filtering irrelevant information is the crucial determining factor, rather than differences in capacity per se. We examined this hypothesis by relating WMC (as measured by complex span tasks) to accuracy and eye movements during visual change detection tasks with different degrees of attentional filtering and allocation requirements. Our results did not indicate strong filtering differences between high- and low-WMC groups, and where differences were observed, they were counter to those predicted by the strongest attentional filtering hypothesis. Bayes factors indicated evidence favoring positive or null relationships between WMC and correct responses to unemphasized information, as well as between WMC and the time spent looking at unemphasized information. These findings are consistent with the hypothesis that individual differences in storage capacity, not only filtering efficiency, underlie individual differences in working memory.

Background: Inflammation during inflammatory bowel disease may alter nutrient availability to adherent mucosal bacteria and impact their metabolic function. Microbial metabolites may regulate intestinal CD4 T-cell homeostasis. We investigated the relationship between inflammation and microbial function by inferred metagenomics of the mucosal microbiota from colonic pinch biopsies of patients with inflammatory bowel disease., Methods: Paired pinch biopsy samples of known inflammation states were analyzed from ulcerative colitis (UC) (23), Crohn's disease (CD) (21), and control (24) subjects by 16S ribosomal sequencing, histopathologic assessment, and flow cytometry. PICRUSt was used to generate metagenomic data and derive relative Kyoto Encyclopedia of Genes and Genomes Pathway abundance information. Leukocytes were isolated from paired biopsy samples and analyzed by multicolor flow cytometry. Active inflammation was defined by neutrophil infiltration into the epithelium., Results: Carriage of metabolic pathways in the mucosal microbiota was relatively stable among patients with inflammatory bowel disease, despite large variations in individual bacterial community structures. However, microbial function was significantly altered in inflamed tissue of UC patients, with a reduction in carbohydrate and nucleotide metabolism in favor of increased lipid and amino acid metabolism. These differences were not observed in samples from CD patients. In CD, microbial lipid, carbohydrate, and amino acid metabolism tightly correlated with the frequency of CD4Foxp3 Tregs, whereas in UC, these pathways correlated with the frequency of CD4IL-22 (TH22) cells., Conclusions: Metabolic pathways of the mucosal microbiota in CD do not vary as much as UC with inflammation state, indicating a more systemic perturbation of host-bacteria interactions in CD compared with more localized dysfunction in UC.

Opportunity has investigated in detail rocks on the rim of the Noachian age Endeavour crater, where orbital spectral reflectance signatures indicate the presence of Fe(+3)-rich smectites. The signatures are associated with fine-grained, layered rocks containing spherules of diagenetic or impact origin. The layered rocks are overlain by breccias, and both units are cut by calcium sulfate veins precipitated from fluids that circulated after the Endeavour impact. Compositional data for fractures in the layered rocks suggest formation of Al-rich smectites by aqueous leaching. Evidence is thus preserved for water-rock interactions before and after the impact, with aqueous environments of slightly acidic to circum-neutral pH that would have been more favorable for prebiotic chemistry and microorganisms than those recorded by younger sulfate-rich rocks at Meridiani Planum.

T helper type (Th17) cytokines such as interleukin (IL)-17A and IL-22 are important in maintaining mucosal barrier function and may be important in the pathogenesis of inflammatory bowel diseases (IBDs). Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantly elevated numbers of IL-17+, CD4+ cells compared with healthy controls and ulcerative colitis (UC) patients, but these numbers did not vary based on the inflammatory status of the mucosa. By contrast, UC patients had significantly reduced numbers of IL-22+ cells in actively inflamed tissues compared with both normal tissue and healthy controls. There was a selective increase in mono-IL-17-producing cells from the mucosa of UC patients with active inflammation together with increased expression of transforming growth factor (TGF)-β and c-Maf. Increasing concentrations of TGF-β in lamina propria mononuclear cell cultures significantly depleted Th22 cells, whereas anti-TGF-β antibodies increased IL-22 production. When mucosal microbiota was examined, depletion of Th22 cells in actively inflamed tissue was associated with reduced populations of Clostridiales and increased populations of Proteobacteria. These results suggest that increased TGF-β during active inflammation in UC may lead to the loss of Th22 cells in the human intestinal mucosa.

Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1β (IL-1β) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of α4β7 and bound HIV envelope in an α4β7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1β (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.

A 38-year-old man with a history of HIV infection virologically suppressed on antiretroviral therapy presents to his gastroenterologist for evaluation of iron deficiency anemia and weight loss. A diagnostic colonoscopy demonstrates a two-centimeter ulcerated mass in the cecum. Biopsies of the lesion return moderately differentiated adenocarcinoma that is wild type for the KRAS mutation by real-time PCR.

TGF-β1 and VEGF, both angiogenesis inducers, have opposing effects on vascular endothelial cells. TGF-β1 induces apoptosis; VEGF induces survival. We have previously shown that TGF-β1 induces endothelial cell expression of VEGF, which mediates TGF-β1 induction of apoptosis through activation of p38 mitogen-activated protein kinase (MAPK). Because VEGF activates p38(MAPK) but protects the cells from apoptosis, this finding suggested that TGF-β1 converts p38(MAPK) signaling from prosurvival to proapoptotic. Four isoforms of p38(MAPK) -α, β, γ, and δ-have been identified. Therefore, we hypothesized that different p38(MAPK) isoforms control endothelial cell apoptosis or survival, and that TGF-β1 directs VEGF activation of p38(MAPK) from a prosurvival to a proapoptotic isoform. Here, we report that cultured endothelial cells express p38α, β, and γ. VEGF activates p38β, whereas TGF-β1 activates p38α. TGF-β1 treatment rapidly induces p38α activation and apoptosis. Subsequently, p38α activation is downregulated, p38β is activated, and the surviving cells become refractory to TGF-β1 induction of apoptosis and proliferate. Gene silencing of p38α blocks TGF-β1 induction of apoptosis, whereas downregulation of p38β or p38γ expression results in massive apoptosis. Thus, in endothelial cells p38α mediates apoptotic signaling, whereas p38β and p38γ transduce survival signaling. TGF-β1 activation of p38α is mediated by VEGF, which in the absence of TGF-β1 activates p38β. Therefore, these results show that TGF-β1 induces endothelial cell apoptosis by shifting VEGF signaling from the prosurvival p38β to the proapoptotic p38α.

The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called 'helminthic therapy') in an effort to mitigate the inflammatory response. In this review, we summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

There is increasing evidence that dysregulation of CD4(+) T cell populations leads to intestinal inflammation, but the regional distribution of these populations throughout the intestinal tract in healthy individuals remains unclear. Here, we show that T(H)17, T(H)22 and T(Reg) cells are enriched in the healthy human cecum compared to the terminal ileum and sigmoid colon, whereas T(H)1 and T(H)2 cells do not significantly vary by location. Transcriptional profiling analysis of paired pinch biopsies from different regions of the intestine identified significant differences in the metabolic state of the terminal ileum, cecum, and sigmoid colon. An increased proportion of T(H)17 cells was positively associated with expression of resistin (RETN) and negatively associated with expression of trefoil factor 1 (TFF1). These results suggest that CD4(+) T helper cells that are important in maintaining mucosal barrier function may be enriched in the cecum as a result of metabolic differences of the surrounding microenvironment.

Rationale: Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds., Objectives: To evaluate viral strain and load in a prospective asthma cohort during a natural cold., Methods: Adults were enrolled at the first sign of a cold, with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. Serial nasal lavage and induced sputum samples were assessed for viral copy number and inflammatory cell counts., Measurements and Main Results: A total of 52 persons with asthma and 14 control subjects without atopy or asthma were studied for over 10 weeks per subject on average; 25 participants developed an asthma exacerbation. Detection of HRVs in the preceding 5 days was the most common attributable exposure related to exacerbation. Compared with other infections, those by a minor group A HRV were 4.4- fold more likely to cause exacerbation (P = 0.038). Overall, sputum neutrophils and the burden of rhinovirus in the lower airway were similar in control subjects without atopy and the asthma group. However, among HRV-infected participants with asthma, exacerbations were associated with greater sputum neutrophil counts (P = 0.005)., Conclusions: HRV infection is a frequent cause of exacerbations in adults with asthma and a cold, and there may be group-specific differences in severity of these events. The absence of large differences in viral burden among groups suggests differential lower airway sensitization to the effects of neutrophilic inflammation in the patients having exacerbations.

Objective: To evaluate impact of the program after up to 6 years of follow-up in survival, virologic, and immunologic response., Methods: Prospective follow-up of patients initiating first highly active antiretroviral therapy from 2001 to 2007. Chile began in 2001 an expanded access program to antiretroviral therapy. The Chilean AIDS Cohort has enrolled >85% of patients from this program in the public health system., Statistical Analysis: χ², Fisher tests, survival, univariate and multivariate analysis., Results: Five thousand one hundred fifteen adults (16% women); median follow-up: 3.64 years (18,159 patient-years). At baseline: median age, 35.8 years; 45.6% had clinical AIDS; median CD4 cell count, 102 cells per cubic millimeter. Global mortality, 9.0%; loss to follow-up, 6.8%. Probability of survival at 1 and 5 years were 0.95 and 0.89, respectively. First regimen was maintained in 72% of those alive and in control at 1 year and 48% at end of study. Main reason for therapy change/discontinuation was drug toxicity (44.9%). At last visit, 74% of active patients had viral suppression, and median CD4 cell count had reached 301 cells per cubic millimeter., Conclusions: In this middle-income country, wide access highly active antiretroviral therapy has been successfully implemented and evaluated. Despite advanced disease at initiation, survival, clinical, virologic, and immunologic outcomes have been comparable with that of industrialized countries.

A hallmark of the immune system is the ability to ignore self-antigens. In attempts to bypass normal immune tolerance, a post-translational protein modification was introduced into self-antigens to break T and B cell tolerance. We demonstrate that immune tolerance is bypassed by immunization with a post-translationally modified melanoma antigen. In particular, the conversion of an aspartic acid to an isoaspartic acid within the melanoma antigen tyrosinase-related protein (TRP)-2 peptide-(181-188) makes the otherwise immunologically ignored TRP-2 antigen immunogenic. Tetramer analysis of iso-Asp TRP-2 peptide-immunized mice demonstrated that CD8+ T cells not only recognized the isoaspartyl TRP-2 peptide but also the native TRP-2 peptide. These CD8+ T cells functioned as cytotoxic T lymphocytes, as they effectively lysed TRP-2 peptide-pulsed targets both in vitro and in vivo. Potentially, post-translational protein modification can be utilized to trigger strong immune responses to either tumor proteins or potentially weakly immunogenic pathogens.

Chile, middle-income country with 15 million people, began an expanded access program (EAP) to antiretroviral therapy (ART) in 2001. EAP provides ART, monitoring, and funding for management of associated complications in 32 points of care. A national cohort (Chilean AIDS Cohort [ChiAC]), enrolling 98% of these patients, was created for standardized treatment and impact evaluation. Information exchange is mainly through the Internet. By December 2004, the ChiAC had 4365 participants (83.3% male). At baseline, 47.5% had clinical AIDS, 26.2% were asymptomatic, 80.2% had a CD4 count <200 cells/mm and 58.2% were ART naive; in these patients, the most frequent regimen is zidovudine, lamivudine, and efavirenz. A 6-month follow-up in 1057 patients showed a global mortality of 5% (0.5% if patients were asymptomatic at baseline and 8.3% if patients had baseline AIDS). There was a similar risk of death if the baseline CD4 count was 100 to 200 cells/mm or >200 cells/mm ( approximately 1%), but this increased to 4.8% (relative risk [RR] = 5.2) and 10.7% (RR = 11.5) if the CD4 count was 51 to 100 cells/mm or

The small martian satellites Phobos and Deimos orbit in synchronous rotation with inclinations of only 0.01 degrees and 0.92 degrees , respectively, relative to the planet's equatorial plane. Thus, an observer at near-equatorial latitudes on Mars could occasionally observe solar eclipses by these satellites (see ref. 1, for example). Because the apparent angular diameter of the satellites is much smaller than that of the Sun, however, such events are more appropriately referred to as transits. Transit data can be used for correcting and refining the orbital ephemerides of the moons. For example, Phobos is known to exhibit a secular acceleration that is caused by tidal dissipation within Mars. Long-term, accurate measurements are needed to refine the magnitude and origin of this dissipation within the martian interior as well as to refine the predicted orbital evolution of both satellites. Here we present observations of six transits of Phobos and Deimos across the solar disk from cameras on Mars aboard the Mars Exploration Rovers Spirit and Opportunity. These are the first direct imaging observations of satellites transiting the Sun from the surface of another planet.

CD19 is a B cell-surface molecule that participates as an important regulatory signaling complex for antigen bound at the surface by Ig. Triggering of CD19 through its linkage with CD21 amplifies signals transduced through the Src family kinases and modulates B cell differentiation in response to antigen. This study examines the kinetics of antigen uptake and processing of antigen directly targeted to the CD19 protein on purified B cells. We have demonstrated that the antigen internalized within minutes through CD19 forms a cap at the B cell surface and can be found within lysosomes in the cytoplasm in 90 min. B cells acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co-stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered intravenously bind B cells in vivo and activate antigen-specific T cells more efficiently than non-specific uptake and in a manner similar to antigen taken up through surface IgM on B cells. This work illustrates an important and previously unrecognized mechanism for targeting proteins to B lymphocytes for antigen presentation and activation of CD4 T cells.

Thermal infrared spectra of the martian atmosphere taken by the Miniature Thermal Emission Spectrometer (Mini-TES) were used to determine the atmospheric temperatures in the planetary boundary layer and the column-integrated optical depth of aerosols. Mini-TES observations show the diurnal variation of the martian boundary layer thermal structure, including a near-surface superadiabatic layer during the afternoon and an inversion layer at night. Upward-looking Mini-TES observations show warm and cool parcels of air moving through the Mini-TES field of view on a time scale of 30 seconds. The retrieved dust optical depth shows a downward trend at both sites.

The Miniature Thermal Emission Spectrometer (Mini-TES) on Opportunity investigated the mineral abundances and compositions of outcrops, rocks, and soils at Meridiani Planum. Coarse crystalline hematite and olivine-rich basaltic sands were observed as predicted from orbital TES spectroscopy. Outcrops of aqueous origin are composed of 15 to 35% by volume magnesium and calcium sulfates [a high-silica component modeled as a combination of glass, feldspar, and sheet silicates (approximately 20 to 30%)], and hematite; only minor jarosite is identified in Mini-TES spectra. Mini-TES spectra show only a hematite signature in the millimeter-sized spherules. Basaltic materials have more plagioclase than pyroxene, contain olivine, and are similar in inferred mineral composition to basalt mapped from orbit. Bounce rock is dominated by clinopyroxene and is close in inferred mineral composition to the basaltic martian meteorites. Bright wind streak material matches global dust. Waterlain rocks covered by unaltered basaltic sands suggest a change from an aqueous environment to one dominated by physical weathering.