Status of the JWST Integrated Science Instrument Module

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Breakthrough capability for the NASA Astrophysics Explorer Program: Reaching the darkest sky

We describe a mission architecture designed to substantially increase the science capability of the NASA Science Mission Directorate (SMD) Astrophysics Explorer Program for all AO proposers working within the near-UV to far-infrared spectrum. We have demonstrated that augmentation of Falcon 9 Explorer launch services with a 13 kW Solar Electric Propulsion (SEP) stage can deliver a 700 kg science observatory payload to extra-Zodiacal orbit. This new capability enables up to ~13X increased photometric sensitivity and ~160X increased observing speed relative to a Sun-Earth L2, Earth-trailing, or Earth orbit with no increase in telescope aperture. All enabling SEP stage technologies for this launch service augmentation have reached sufficient readiness (TRL-6) for Explorer Program application in conjunction with the Falcon 9. We demonstrate that enabling Astrophysics Explorers to reach extra-zodiacal orbit will allow this small payload program to rival the science performance of much larger long development time systems; thus, providing a means to realize major science objectives while increasing the SMD Astrophysics portfolio diversity and resiliency to external budget pressure. The SEP technology employed in this study has strong applicability to SMD Planetary Science community-proposed missions. SEP is a stated flight demonstration priority for NASA's Office of the Chief Technologist (OCT). This new mission architecture for astrophysics Explorers enables an attractive realization of joint goals for OCT and SMD with wide applicability across SMD science disciplines.Comment: Submitted to proceedings of the SPIE Astronomical Telescopes and Instrumentation conference, Amsterdam, The Netherlands, July 201

Milliarcsecond N-Band Observations of the Nova RS Ophiuchi: First Science with the Keck Interferometer Nuller

We report observations of the nova RS Ophiuchi (RS Oph) using the Keck Interferometer Nuller (KIN), approximately 3.8 days following the most recent outburst that occurred on 2006 February 12. These observations represent the first scientific results from the KIN, which operates in N-band from 8 to 12.5 microns in a nulling mode. By fitting the unique KIN data, we have obtained an angular size of the mid-infrared continuum of 6.2, 4.0, or 5.4 mas for a disk profile, gaussian profile (FWHM), and shell profile respectively. The data show evidence of enhanced neutral atomic hydrogen emission and atomic metals including silicon located in the inner spatial regime near the white dwarf (WD) relative to the outer regime. There are also nebular emission lines and evidence of hot silicate dust in the outer spatial region, centered at ! 17 AU from the WD, that are not found in the inner regime. Our evidence suggests that these features have been excited by the nova flash in the outer spatial regime before the blast wave reached these regions. These identifications support a model in which the dust appears to be present between outbursts and is not created during the outburst event. We further discuss the present results in terms of a unifying model of the system that includes an increase in density in the plane of the orbit of the two stars created by a spiral shock wave caused by the motion of the stars through the cool wind of the red giant star. These data show the power and potential of the nulling technique which has been developed for the detection of Earth-like planets around nearby stars for the Terrestrial Planet Finder Mission and Darwin missions.Comment: 41 pages, 10 figure

Changing antimalarial drug resistance patterns identified by surveillance at three sites in Uganda.

: We assessed Plasmodium falciparum drug resistance markers in parasites collected in 2012, 2013, and 2015 at 3 sites in Uganda. The prevalence and frequency of parasites with mutations in putative transporters previously associated with resistance to aminoquinolines, but increased sensitivity to lumefantrine (pfcrt 76T; pfmdr1 86Y and 1246Y), decreased markedly at all sites. Antifolate resistance mutations were common, with apparent emergence of mutations (pfdhfr 164L; pfdhps 581G) associated with high-level resistance. K13 mutations linked to artemisinin resistance were uncommon and did not increase over time. Changing malaria treatment practices have been accompanied by profound changes in markers of resistance.<br/

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Toward the unity of pathological and exertional fatigue: a predictive processing model

Fatigue is a common experience in both health and disease. Yet, pathological (i.e., prolonged or chronic) and transient (i.e., exertional) fatigue symptoms are traditionally considered distinct, compounding a separation between interested research fields within the study of fatigue. Within the clinical neurosciences, nascent frameworks position pathological fatigue as a product of inference derived through hierarchical predictive processing. The metacognitive theory of dyshomeostasis (Stephan et al., 2016) states that pathological fatigue emerges from the metacognitive mechanism in which the detection of persistent mismatches between prior interoceptive predictions and ascending sensory evidence (i.e., prediction error) signals low evidence for internal generative models, which undermine an agent’s feeling of mastery over the body and is thus experienced phenomenologically as fatigue. Although acute, transient subjective symptoms of exertional fatigue have also been associated with increasing interoceptive prediction error, the dynamic computations that underlie its development have not been clearly defined. Here, drawing on the metacognitive theory of dyshomeostasis, we extend this account to offer an explicit description of the development of fatigue during extended periods of (physical) exertion. Accordingly, it is proposed that a loss of certainty or confidence in control predictions in response to persistent detection of prediction error features as a common foundation for the conscious experience of both pathological and nonpathological fatigue

Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Malaria: A Randomized Trial

OBJECTIVES: To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda. DESIGN: Randomized single-blinded clinical trial. SETTING: Apac, Uganda, an area of very high malaria transmission intensity. PARTICIPANTS: Children aged 6 mo to 10 y with uncomplicated falciparum malaria. INTERVENTION: Treatment of malaria with AL or DP, each following standard 3-d dosing regimens. OUTCOME MEASURES: Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS: Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%-26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%-19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%-12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%-16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs. CONCLUSION: DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity