The Spitzer Survey of the Small Magellanic Cloud: Discovery of Embedded Protostars in the HII Region NGC 346

We use Spitzer Space Telescope observations from the Spitzer Survey of the Small Magellanic Cloud (S3MC) to study the young stellar content of N66, the largest and brightest HII region in the SMC. In addition to large numbers of normal stars, we detect a significant population of bright, red infrared sources that we identify as likely to be young stellar objects (YSOs). We use spectral energy distribution (SED) fits to classify objects as ordinary (main sequence or red giant) stars, asymptotic giant branch stars, background galaxies, and YSOs. This represents the first large-scale attempt at blind source classification based on Spitzer SEDs in another galaxy. We firmly identify at least 61 YSOs, with another 50 probable YSOs; only one embedded protostar in the SMC was reported in the literature prior to the S3MC. We present color selection criteria that can be used to identify a relatively clean sample of YSOs with IRAC photometry. Our fitted SEDs indicate that the infrared-bright YSOs in N66 have stellar masses ranging from 2 Msun to 17 Msun, and that approximately half of the objects are Stage II protostars, with the remaining YSOs roughly evenly divided between Stage I and Stage III sources. We find evidence for primordial mass segregation in the HII region, with the most massive YSOs being preferentially closer to the center than lower-mass objects. Despite the low metallicity and dust content of the SMC, the observable properties of the YSOs appear consistent with those in the Milky Way. Although the YSOs are heavily concentrated within the optically bright central region of N66, there is ongoing star formation throughout the complex and we place a lower limit on the star formation rate of 3.2 x 10^-3 Msun/yr over the last ~1 Myr.Comment: 13 pages, 5 figures (3 in color), 2 tables. Accepted for publication in Ap

Heart failure around the world

With increasingly large sample sizes required to demonstrate event reduction, heart failure outcome trials are no longer being performed in a small group of selected patients and countries, but at a global scale with worldwide contribution of patients from countries with considerable differences in background therapy, socioeconomic status and healthcare practices. Recent studies have highlighted how socioeconomic determinants rather than geographical factors may underlie the heterogeneity of patient populations across the globe. Therefore, in this review, we evaluated (i) regional differences in patient characteristics and outcomes in recent epidemiologic studies; (ii) regional differences in worldwide representativeness of clinical trial populations; and (iii) the role of socioeconomic determinants in driving country differences in heart failure trial enrolment and clinical outcomes

Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: a case report

Introduction Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear. Case presentation A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis. Conclusion In this case report, we present the finding of cardiac tissue metabolomics, which may indicate a problem with vasodilation as a contributor to cardiac death in diffuse systemic sclerosis. The use of autopsy and tissue metabolomics in rare disease may help clarify disease pathogenesis

Temporal Elements in Career Selection Decisions: An Archival Study Investigating Career Decisions in Medicine

T ime is a ubiquitous but often omitted variable in career selection decisions. This study investigates the impact of temporal elements on career selection decisions, thus advancing our understanding of both career decision making and the impact of timing on decision making. We investigate the influence of timing and duration of experience with career options on career selection decisions in an archival study using medical residents' rotation schedules. We also investigate factors that mitigate the influence of timing on career selection decisions by examining the interaction of timing with the duration of experience and the diversity of options that an individual experiences. Conditional logit results indicate that decisions often based on career and individual attributes are significantly influenced by the timing and duration of options even when controlling for option attributes. Additionally, significant interactions between timing and diversity of experience and timing and duration of experience revealed boundary conditions for timing. Individuals were more likely to select later-appearing career options when they appeared for a greater duration or when they experienced a greater diversity of options in their schedule. Results illustrate that schedules over which individuals have no control can influence consequential decisions

Mass drug administration for malaria

Background Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published. Objectives Primary objectives To assess the sustained effect of MDA with antimalarial drugs on: ‐ the reduction in malaria transmission in moderate‐ to high‐transmission settings; ‐ the interruption of transmission in very low‐ to low‐transmission settings. Secondary objective To summarize the risk of drug‐associated adverse effects following MDA. Search methods We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) and non‐randomized studies comparing MDA to no MDA with balanced co‐interventions across study arms and at least two geographically distinct sites per study arm. Data collection and analysis Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no‐MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster‐randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coefficient. We assessed the certainty of the evidence using the GRADE approach. For non‐randomized controlled before‐and‐after (CBA) studies, we summarized the data using difference‐in‐differences (DiD) analyses. Main results Thirteen studies met our criteria for inclusion. Ten were cRCTs and three were CBAs. Cluster‐randomized controlled trials Moderate‐ to high‐endemicity areas (prevalence ≥ 10%) We included data from two studies conducted in The Gambia and Zambia. At one to three months after MDA, the Plasmodium falciparum (hereafter, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no effect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low‐certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate‐certainty evidence); and confirmed malaria illness incidence may be substantially lower, but the CIs included no effect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low‐certainty evidence). At four to six months after MDA, MDA showed little or no effect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate‐certainty evidence) and, no persisting effect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low‐ to low‐endemicityareas (prevalence < 10%) Seven studies from Cambodia, Laos, Myanmar (two studies), Vietnam, Zambia, and Zanzibar evaluated the effects of multiple rounds of MDA on P falciparum. Immediately following MDA (less than one month after MDA), parasitaemia prevalence was reduced (RR 0.12, 95% CI 0.03 to 0.52; one study; low‐certainty evidence). At one to three months after MDA, there was a reduction in both parasitaemia incidence (rate ratio 0.37, 95% CI 0.21 to 0.55; 1 study; moderate‐certainty evidence) and prevalence (RR 0.25, 95% CI 0.15 to 0.41; 7 studies; low‐certainty evidence). For confirmed malaria incidence, absolute rates were low, and it is uncertain whether MDA had an effect on this outcome (rate ratio 0.58, 95% CI 0.12 to 2.73; 2 studies; very low‐certainty evidence). For P falciparum prevalence, the relative differences declined over time, from RR 0.63 (95% CI 0.36 to 1.12; 4 studies) at four to six months after MDA, to RR 0.86 (95% CI 0.55 to 1.36; 5 studies) at 7 to 12 months after MDA. Longer‐term prevalence estimates showed overall low absolute risks, and relative effect estimates of the effect of MDA on prevalence varied from RR 0.82 (95% CI 0.20 to 3.34) at 13 to 18 months after MDA, to RR 1.25 (95% CI 0.25 to 6.31) at 31 to 36 months after MDA in one study. Five studies from Cambodia, Laos, Myanmar (2 studies), and Vietnam evaluated the effect of MDA on Plasmodium vivax (hereafter, P vivax). One month following MDA, P vivax prevalence was lower (RR 0.18, 95% CI 0.08 to 0.40; 1 study; low‐certainty evidence). At one to three months after MDA, there was a reduction in P vivax prevalence (RR 0.15, 95% CI 0.10 to 0.24; 5 studies; low‐certainty evidence). The immediate reduction on P vivax prevalence was not sustained over time, from RR 0.78 (95% CI 0.63 to 0.95; 4 studies) at four to six months after MDA, to RR 1.12 (95% CI 0.94 to 1.32; 5 studies) at 7 to 12 months after MDA. One of the studies in Myanmar provided estimates of longer‐term effects, where overall absolute risks were low, ranging from RR 0.81 (95% CI 0.44 to 1.48) at 13 to 18 months after MDA, to RR 1.20 (95% CI 0.44 to 3.29) at 31 to 36 months after MDA. Non‐randomized studies Three CBA studies were conducted in moderate‐ to high‐transmission areas in Burkina Faso, Kenya, and Nigeria. There was a reduction in P falciparum parasitaemia prevalence in MDA groups compared to control groups during MDA (DiD range: ‐15.8 to ‐61.4 percentage points), but the effect varied at one to three months after MDA (DiD range: 14.9 to ‐41.1 percentage points). Authors' conclusions In moderate‐ to high‐transmission settings, no studies reported important effects on P falciparum parasitaemia prevalence within six months after MDA. In very low‐ to low‐transmission settings, parasitaemia prevalence and incidence were reduced initially for up to three months for both P falciparum and P vivax; longer‐term data did not demonstrate an effect after four months, but absolute risks in both intervention and control groups were low. No studies provided evidence of interruption of malaria transmission

Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants

© 2017 2017 International Pediatric Research Foundation, Inc. BackgroundLongitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.MethodsDuring 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUC VL).ResultsThe 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUC VL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were rebound; likely representing viral mutational immune escape

The Spitzer Survey of the Small Magellanic Cloud: S3MC Imaging and Photometry in the Mid- and Far-Infrared Wavebands

We present the initial results from the Spitzer Survey of the Small Magellanic Cloud (S3MC), which imaged the star-forming body of the Small Magellanic Cloud (SMC) in all seven MIPS and IRAC wavebands. We find that the F_8/F_24 ratio (an estimate of PAH abundance) has large spatial variations and takes a wide range of values that are unrelated to metallicity but anticorrelated with 24 um brightness and F_24/F_70 ratio. This suggests that photodestruction is primarily responsible for the low abundance of PAHs observed in star-forming low-metallicity galaxies. We use the S3MC images to compile a photometric catalog of ~400,000 mid- and far-infrared point sources in the SMC. The sources detected at the longest wavelengths fall into four main categories: 1) bright 5.8 um sources with very faint optical counterparts and very red mid-infrared colors ([5.8]-[8.0]>1.2), which we identify as YSOs. 2) Bright mid-infrared sources with mildly red colors (0.16<[5.8]-[8.0]<0.6), identified as carbon stars. 3) Bright mid-infrared sources with neutral colors and bright optical counterparts, corresponding to oxygen-rich evolved stars. And, 4) unreddened early B stars (B3 to O9) with a large 24 um excess. This excess is reminiscent of debris disks, and is detected in only a small fraction of these stars (<5%). The majority of the brightest infrared point sources in the SMC fall into groups one to three. We use this photometric information to produce a catalog of 282 bright YSOs in the SMC with a very low level of contamination (~7%).Comment: Accepted for publication in The Astrophysical Journal. Given the draconian figure file-size limits implemented in astro-ph, readers are encouraged to download the manuscript with full quality images from http://celestial.berkeley.edu/spitzer/publications/s3mcsurvey.pd

Genetic diversity of Plasmodium falciparum parasite by microsatellite markers after scale-up of insecticide-treated bed nets in western Kenya

Background: An initial study of genetic diversity of Plasmodium falciparum in Asembo, western Kenya showed that the parasite maintained overall genetic stability 5 years after insecticide-treated bed net (ITN) introduction in 1997. This study investigates further the genetic diversity of P. falciparum 10 years after initial ITN introduction in the same study area and compares this with two other neighbouring areas, where ITNs were introduced in 1998 (Gem) and 2004 (Karemo). Methods: From a cross-sectional survey conducted in 2007, 235 smear-positive blood samples collected from children ≤15-year-old in the original study area and two comparison areas were genotyped employing eight neutral microsatellites. Differences in multiple infections, allele frequency, parasite genetic diversity and parasite population structure between the three areas were assessed. Further, molecular data reported previously (1996 and 2001) were compared to the 2007 results in the original study area Asembo. Results: Overall proportion of multiple infections (M A ) declined with time in the original study area Asembo (from 95.9 %-2001 to 87.7 %-2007). In the neighbouring areas, M A was lower in the site where ITNs were introduced in 1998 (Gem 83.7 %) compared to where they were introduced in 2004 (Karemo 96.7 %) in 2007. Overall mean allele count (M AC ~ 2.65) and overall unbiased heterozygosity (H e ~ 0.77) remained unchanged in 1996, 2001 and 2007 in Asembo and was the same level across the two neighbouring areas in 2007. Overall parasite population differentiation remained low over time and in the three areas at F ST < 0.04. Both pairwise and multilocus linkage disequilibrium showed limited to no significant association between alleles in Asembo (1996, 2001 and 2007) and between three areas. Conclusions: This study showed the P. falciparum high genetic diversity and parasite population resilience on samples collected 10 years apart and in different areas in western Kenya. The results highlight the need for long-term molecular monitoring after implementation and use of combined and intensive prevention and intervention measures in the region

Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

BACKGROUND: Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. RESULTS: 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection