Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity.

Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking. Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly-confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia. Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538-8481/μL]) than in falciparum (9600/μL; P 15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P 15000/μL

Clearance of human IgG1-sensitised red blood cells in vivo in humans relates to the in vitro properties of antibodies from alternative cell lines.

We previously produced a recombinant version of the human anti-RhD antibody Fog-1 in the rat myeloma cell line, YB2/0. When human, autologous RhD-positive red blood cells (RBC) were sensitised with this IgG1 antibody and re-injected, they were cleared much more rapidly from the circulation than had been seen earlier with the original human-mouse heterohybridoma-produced Fog-1. Since the IgG have the same amino acid sequence, this disparity is likely to be due to alternative glycosylation that results from the rat and mouse cell lines. By comparing the in vitro properties of YB2/0-produced Fog-1 IgG1 and the same antibody produced in the mouse myeloma cell line NS0, we now have a unique opportunity to pinpoint the cause of the difference in ability to clear RBC in vivo. Using transfected cell lines that express single human FcγR, we showed that IgG1 made in YB2/0 and NS0 cell lines bound equally well to receptors of the FcγRI and FcγRII classes but that the YB2/0 antibody was superior in FcγRIII binding. When measuring complexed IgG binding, the difference was 45-fold for FcγRIIIa 158F, 20-fold for FcγRIIIa 158V and approximately 40-fold for FcγRIIIb. The dissimilarity was greater at 100-fold in monomeric IgG binding assays with FcγRIIIa. When used to sensitise RBC, the YB2/0 IgG1 generated 100-fold greater human NK cell antibody-dependent cell-mediated cytotoxicity and had a 103-fold advantage over the NS0 antibody in activating NK cells, as detected by CD54 levels. In assays of monocyte activation and macrophage adherence/phagocytosis, where FcγRI plays major roles, RBC sensitised with the two antibodies produced much more similar results. Thus, the alternative glycosylation profiles of the Fog-1 antibodies affect only FcγRIII binding and FcγRIII-mediated functions. Relating this to the in vivo studies confirms the importance of FcγRIII in RBC clearance.The work was supported by funding from the Department of Pathology, University of Cambridge through income that was derived from commercial exploitation of patented antibodies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109463

3C 220.3: a radio galaxy lensing a submillimeter galaxy

Herschel Space Observatory photometry and extensive multiwavelength followup have revealed that the powerful radio galaxy 3C 220.3 at z=0.685 acts as a gravitational lens for a background submillimeter galaxy (SMG) at z=2.221. At an observed wavelength of 1mm, the SMG is lensed into three distinct images. In the observed near infrared, these images are connected by an arc of 1.8" radius forming an Einstein half-ring centered near the radio galaxy. In visible light, only the arc is apparent. 3C 220.3 is the only known instance of strong galaxy-scale lensing by a powerful radio galaxy not located in a galaxy cluster and therefore it offers the potential to probe the dark matter content of the radio galaxy host. Lens modeling rejects a single lens, but two lenses centered on the radio galaxy host A and a companion B, separated by 1.5", provide a fit consistent with all data and reveal faint candidates for the predicted fourth and fifth images. The model does not require an extended common dark matter halo, consistent with the absence of extended bright X-ray emission on our Chandra image. The projected dark matter fractions within the Einstein radii of A (1.02") and B (0.61") are about 0.4 +/- 0.3 and 0.55 +/- 0.3. The mass to i-band light ratios of A and B, M/L ~ 8 +/- 4 Msun/Lsun, appear comparable to those of radio-quiet lensing galaxies at the same redshift in the CASTLES, LSD, and SL2S samples. The lensed SMG is extremely bright with observed f(250um) = 440mJy owing to a magnification factor mu~10. The SMG spectrum shows luminous, narrow CIV 154.9nm emission, revealing that the SMG houses a hidden quasar in addition to a violent starburst. Multicolor image reconstruction of the SMG indicates a bipolar morphology of the emitted ultraviolet (UV) light suggestive of cones through which UV light escapes a dust-enshrouded nucleus.Comment: 17 pages, 14 Figures, accepted for publication in Ap

Atlas of quasar energy distributions

We present an atlas of the spectral energy distributions (SEDs) of normal, nonblazar, quasars over the whole available range (radio to 10 keV X-rays) of the electromagnetic spectrum. The primary (UVSX) sample includes 47 quasars for which the spectral energy distributions include X-ray spectral indices and UV data. Of these, 29 are radio quiet, and 18 are radio loud. The SEDs are presented both in figures and in tabular form, with additional tabular material published on CD-ROM. Previously unpublished observational data for a second set of quasars excluded from the primary sample are also tabulated. The effects of host galaxy starlight contamination and foreground extinction on the UVSX sample are considered and the sample is used to investigate the range of SED properties. Of course, the properties we derive are influenced strongly by the selection effects induced by quasar discovery techniques. We derive the mean energy distribution (MED) for radio-loud and radio-quiet objects and present the bolometric corrections derived from it. We note, however, that the dispersion about this mean is large (approximately one decade for both the infrared and ultraviolet components when the MED is normalized at the near-infrared inflection). At least part of the dispersion in the ultraviolet may be due to time variability, but this is unlikely to be important in the infrared. The existence of such a large dispersion indicates that the MED reflects only some of the properties of quasars and so should be used only with caution.Astronom

A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB

Healthcare Reform and the Next Generation: United States Medical Student Attitudes toward the Patient Protection and Affordable Care Act

CONTEXT: Over one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented. OBJECTIVE: To evaluate medical students' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost. DESIGN, SETTING, AND PARTICIPANTS: An anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October-December 2010, with 1232 students responding and a response rate of 18%. MAIN OUTCOME MEASURES: Medical students' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items. RESULTS: Of medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided. CONCLUSION: The overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment

Functional diversity and community assembly of river invertebrates show globally consistent responses to decreasing glacier cover

Global change threatens invertebrate biodiversity and its central role in numerous ecosystem functions and services. Functional trait analyses have been advocated to uncover global mechanisms behind biodiversity responses to environmental change, but the application of this approach for invertebrates is underdeveloped relative to other organism groups. From an evaluation of 363 records comprising >1.23 million invertebrates collected from rivers across nine biogeographic regions on three continents, consistent responses of community trait composition and diversity to replicated gradients of reduced glacier cover are demonstrated. After accounting for a systematic regional effect of latitude, the processes shaping river invertebrate functional diversity are globally consistent. Analyses nested within individual regions identified an increase in functional diversity as glacier cover decreases. Community assembly models demonstrated that dispersal limitation was the dominant process underlying these patterns, although environmental filtering was also evident in highly glacierized basins. These findings indicate that predictable mechanisms govern river invertebrate community responses to decreasing glacier cover globally.This work was funded by the following organisations: The UK Natural Environment Research Council grants and studentships GR9/2913, NE/E003729/1, NE/E004539/1, NE/E004148/1, 20 NE/G523963/1, NER/S/A/2003/11192, and NE/L002574/1; the European Union Environment and Climate Programme Arctic and Alpine Stream Ecosystem Research (AASER) project (ENV-CT95-0164); EU-FP7 Assessing Climate impacts on the Quality and quantity of WAter (ACQWA) project (212250); Icelandic Research Council (954890095, 954890096); University of Iceland Research Fund (GMG96, GMG97, GMG98), Wyoming Center for Environmental Hydrology and Geophysics-National Science Foundation (1208909); USA-Wyoming NASA Space Grant Faculty Research Initiation (#NNX10A095H); USA-NSF Wyoming Epscor; Nationalpark Hohe Tauern, Austria; the Royal Society (International Outgoing Grant 2006/R4); the Leverhulme Trust; the Universities of Leeds, Birmingham, Iceland and Innsbruck; European Centre for Arctic Environmental Research (ARCFAC): a Research Infrastructures Action of the European Community FP6 (026129-2008- 72); the Stelvio National Park (2000-2001); the Autonomous Province of Trento (HIGHEST project, 2001-2004, del. PAT n. 1060/2001; VETTA project, 2003-2006, del. PAT n. 3402/2002); MUSE-Museo delle Scienze. We are grateful to Russell Taylor and Mike Winterbourn at the University of Canterbury, NZ, who helped to collect NZ invertebrate data and assisted with identification, and to Hakon Adalsteinsson who contributed to data collection in Iceland. Many other people, too numerous to mention, assisted with fieldwork at all of the study locations. The European Science Foundation sponsored an exploratory ┘ﾗヴﾆゲｴﾗヮ WﾐデｷデﾉWS さGﾉ;IｷWヴ-fed rivers, hydroecology and climate change: current knowledge and future network of monitoring sites (GLAC-HYDROECO-NETぶざ デｴ;デ ┘;ゲ ｴWﾉS ｷﾐ Birmingham, UK in September of 2013 where some of the ideas in this paper were first discussedPeer Reviewe

The Spectral Energy Distributions of Red Two Micron All Sky Survey Active Galactic Nuclei

We present infrared (IR) to X-ray spectral energy distributions (SEDs) for 44 red active galactic nuclei (AGNs) selected from the Two Micron All Sky Survey (2MASS) survey on the basis of their red J − KS color (> 2 mag) and later observed by Chandra. In comparison with optically-, radio-, and X-ray-selected AGNs, their median SEDs are red in the optical and near-IR (NIR) with little/no blue bump. Comparison of the various broadband luminosity ratios shows that the main differences lie at the blue end of the optical and in the NIR to far-IR ratios (when available), with the red 2MASS AGNs being redder than the other samples. It thus seems that NIR color selection isolates the reddest subset of AGNs that can be classified optically. The shape of the SEDs is generally consistent with modest absorption by gas (in the X-ray) and dust (in the optical–IR), as demonstrated by comparing the optical and NIR colors with a reddened median SED and observed optical+NIR to intrinsic X-ray ratios. The levels of obscuration, estimated from X-rays, far-IR, and our detailed optical/NIR color modeling, are all consistent implying NH few × 1022 cm−2. We present SED models that show how the AGN optical/NIR colors change due to differing amounts of reddening, AGN to host galaxy ratio, redshift, and scattered light emission, and apply them to the sources in the sample. We find that the 2MASS AGN optical color, B − R, and to a lesser extent the NIR color, J − KS, are strongly affected by reddening, host galaxy emission, redshift, and in few, highly polarized objects also by scattered AGN light (<2% of intrinsic AGN light in the R band is scattered; this contribution becomes significant as the direct AGN light is absorbed). The lack of low equivalent widths in the distribution of the [O iii] λ5007 emission line implies a predominance of inclined objects in the red 2MASS sample. The obscuration/ inclination of the AGN allows us to see weaker emission components which are generally swamped by the AGN.Astronom

Educating Health Professionals about Drug and Device Promotion: Advocates' Recommendations

Mansfield and colleagues outline the recommendations from four advocacy groups for improving the education of health professionals on promotion of drugs and devices