Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone

Internet-Based Data Collection: Promises and Realities

The use of Internet to aid research practice has become more popular in the recent years. In fact, some believe that Internet surveying and electronic data collection may revolutionize many disciplines by allowing for easier data collection, larger samples, and therefore more representative data. However, others are skeptical of its usability as well as its practical value. The paper highlights both positive and negative outcomes experienced in a number of e-research projects, focusing on several common mistakes and difficulties experienced by the authors. The discussion focuses on ethics and review board issues, recruitment and sampling techniques, technological issues and errors, and data collection, cleaning, and analysis

The First In Situ Encounter of Gigantura chuni (Giganturidae: Giganturoidei: Aulopiformes: Cyclosquamata: Teleostei), with a Preliminary Investigation of Pair-Bonding

The Gulf of Mexico Scientific and Environmental ROV Partnership using Existing iNdustrial Technology (Gulf SERPENT) Project utilizes industrial work-class ROVs based at oceanic oil and gas facilities for scientific research and exploration. During Gulf SERPENT operations, an ROV documented the first in situ observations of Gigantura chuni at a depth of approximately 900 m in the northern Gulf of Mexico. The fish were identified to genus by the length of the caudal fin ventral lobe relative to standard length, reflectance from crystalline guanine, and relative mouth size to the head length. The width-length ratios suggest G. chuni as the species (approximately 1:5 for adult G. chuni vs. 1:10 for adult G. indica). The videos provided the second known in situ observation of giganturids and the first of G. chuni. The first video clearly shows two individuals in close proximity, with both oriented vertically in the water column; a second video clip shows a single individual at a slightly shallower depth, and also oriented vertically in the water column. An odds ratio comparison for collections of G. chuni and G. indica from the DEEPEND program to fitted theoretical distributions was used to preliminarily analyze the probability of encountering various numbers of individuals in a single-sample effort. Groups of two individuals, and in particular even number groupings, were encountered during the DEEPEND program sampling more often than would be expected based on theoretical distributions for both G. chuni and G. indica suggesting pair-bonding may be a likely reproductive strategy complementing synchronous hermaphroditism in giganturids

Manned Lunar Missions: An Exercise in Propulsion Trades and Sensitivities

A recent study performed for the In-Space Propulsion Technology Office at the Marshall Space Flight Center investigated the effects of using different propellant types on the different stages required to perform a manned lunar mission. The original study included investigations into propellant type, propellant storage technology options and sensitivities to specific impulse variations for a lunar orbit rendezvous mission. The initial mission characteristics were based on previous work led by Langley Research Center. Outlined in this paper are the results of that study and the work that followed. A lunar direct return architecture was added to the analysis. Since both architectures required assembly of the various propulsive stages in low Earth orbit and multiple launches to deliver those stages, investigations of launch sequence and scheduling sensitivities were also included. Results show that lunar direct return architectures require more mass to complete missions when compared to lunar orbit rendezvous missions. Within the given architectures, trends in the results tended to be very similar with the architectures indicating very little sensitivity to launch sequence and specific impulse variations and indicating more sensitivity to the propellant choice made for each stage and the time between launches. Even though this study investigates a small subset of the possible lunar architecture trade space, it does begin to outline some of the issues that must be investigated and the characteristics of the mission and the mission elements that are of most importance to a full architecture assessment

Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

The Landscape of Videofluoroscopy in the UK: A Web-Based Survey

Videofluoroscopy (VFS) is considered one of the gold-standard assessments of swallowing. Whilst guidelines for the application and conduct of VFS exist, their translation into clinical practice remain challenging. To build a greater understanding on how VFS clinics operate in the UK. A web-based survey was shared with speech and language therapists (SLTs) working in VFS clinics via professional networks and social media from October 2018 to January 2019. 101 responses were received. Two thirds of clinics were SLT-led, with the majority of clinics being run by two SLTs (73.6%) and a radiographer (95.5%) also known as radiologic technologists, diagnostic radiographers and medical radiation technologists. Less than 50% of radiographers had received specialist training. Around half of the clinics used a standard assessment or analysis protocol and 88.1% a rating scale. Set recipes for a range of textures were used in 53.4% of VFS clinics. Barium and water soluble contrasts were used, but only 15.8% knew the concentration of contrast used. The most commonly reported VFS pulse and frame rate was 15 per second. There was evidence of a lack of SLT knowledge regarding technical operation of VFS. Screening times varied from 0.7–10 min (median 3 min, IQR 2.5–3.5). Around 50% of respondents reported quality issues affecting analysis. In a survey of UK SLTs, translation of VFS guidance into practice was found to be limited which may impact on the quality of assessment and analysis. Collaboration with radiology, strengthening of guidelines and greater uptake of specialist training is deemed essential

Determining dominant scatterers of sound in mixed zooplankton populations

Author Posting. © Acoustical Society of America, 2007. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 122 (2007): 3304-3326, doi:10.1121/1.2793613.High-frequency acoustic scattering techniques have been used to investigate dominant scatterers in mixed zooplankton populations. Volume backscattering was measured in the Gulf of Maine at 43, 120, 200, and 420 kHz. Zooplankton composition and size were determined using net and video sampling techniques, and water properties were determined using conductivity, temperature, and depth sensors. Dominant scatterers have been identified using recently developed scattering models for zooplankton and microstructure. Microstructure generally did not contribute to the scattering. At certain locations, gas-bearing zooplankton, that account for a small fraction of the total abundance and biomass, dominated the scattering at all frequencies. At these locations, acoustically inferred size agreed well with size determined from the net samples. Significant differences between the acoustic, net, and video estimates of abundance for these zooplankton are most likely due to limitations of the net and video techniques. No other type of biological scatterer ever dominated the scattering at all frequencies. Copepods, fluid-like zooplankton that account for most of the abundance and biomass, dominated at select locations only at the highest frequencies. At these locations, acoustically inferred abundance agreed well with net and video estimates. A general approach for the difficult problem of interpreting high-frequency acoustic scattering in mixed zooplankton populations is described.This research was supported in part by the U.S. GLOBEC program, NOAA (Grant nos. NA17RJ1223 and NA67RJ0148), the James S. Cole and Cecily C. Selby Endowed Funds, the Penzance Endowed Fund for Support of Assistant Scientists, and the Adams Chair at the Woods Hole Oceanographic Institution. A selected number of focused experiments were also funded by the ONR (Grant No. N00014-98-1-0362)