Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with AIDS.

Pneumocystis jirovecii pneumonia (PCP) typically presents as an interstitial and alveolar process with ground glass opacities on chest computed tomography (CT). The absence of ground glass opacities on chest CT is thought to have a high negative predictive value for PCP in individuals with AIDS. Here, we report a case of PCP in a man with AIDS who presented to our hospital with subacute shortness of breath and a nonproductive cough. While his chest CT revealed diffuse nodular rather than ground glass opacities, bronchoscopy with bronchoalveolar lavage and transbronchial biopsies confirmed the diagnosis of PCP and did not identify additional pathogens. PCP was not the expected diagnosis based on chest CT, but it otherwise fit well with the patient's clinical and laboratory presentation. In the era of combination antiretroviral therapy, routine prophylaxis for PCP, and increased use of computed tomography, it may be that PCP will increasingly present with nonclassical chest radiographic patterns. Clinicians should be aware of this presentation when selecting diagnostic and management strategies

Laboratory Focus on Improving the Culture of Biosafety: Statewide Risk Assessment of Clinical Laboratories That Process Specimens for Microbiologic Analysis

The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting

Dust Production and Mass Loss in the Galactic Globular Cluster NGC 362

We investigate dust production and stellar mass loss in the Galactic globular cluster NGC 362. Due to its close proximity to the Small Magellanic Cloud (SMC), NGC 362 was imaged with the IRAC and MIPS cameras onboard the Spitzer Space Telescope as part of the Surveying the Agents of Galaxy Evolution (SAGE-SMC) Spitzer Legacy program. We detect several cluster members near the tip of the Red Giant Branch that exhibit infrared excesses indicative of circumstellar dust and find that dust is not present in measurable quantities in stars below the tip of the Red Giant Branch. We modeled the spectral energy distribution (SED) of the stars with the strongest IR excess and find a total cluster dust mass-loss rate of 3.0(+2.0/-1.2) x 10^-9 solar masses per year, corresponding to a gas mass-loss rate of 8.6(+5.6/-3.4) x 10^-6 solar masses per year, assuming [Fe/H] = -1.16. This mass loss is in addition to any dust-less mass loss that is certainly occurring within the cluster. The two most extreme stars, variables V2 and V16, contribute up to 45% of the total cluster dust-traced mass loss. The SEDs of the more moderate stars indicate the presence of silicate dust, as expected for low-mass, low-metallicity stars. Surprisingly, the SED shapes of the stars with the strongest mass-loss rates appear to require the presence of amorphous carbon dust, possibly in combination with silicate dust, despite their oxygen-rich nature. These results corroborate our previous findings in omega Centauri.Comment: 13 pages, 11 figures. Accepted to Ap

Use of controlled low dose gamma irradiation to sterilize allograft tendons for ACL reconstruction: biomechanical and clinical perspective

As reviewed here, numerous biomechanical and clinical studies support the use of controlled, low temperature irradiation of allograft tendons, to provide both excellent clinical results and medical-device grade sterile allografts with minimal risk of disease transmission

Active megadetachment beneath the western United States

Geodetic data, interpreted in light of seismic imaging, seismicity, xenolith studies, and the late Quaternary geologic history of the northern Great Basin, suggest that a subcontinental-scale extensional detachment is localized near the Moho. To first order, seismic yielding in the upper crust at any given latitude in this region occurs via an M7 earthquake every 100 years. Here we develop the hypothesis that since 1996, the region has undergone a cycle of strain accumulation and release similar to “slow slip events” observed on subduction megathrusts, but yielding occurred on a subhorizontal surface 5–10 times larger in the slip direction, and at temperatures >800°C. Net slip was variable, ranging from 5 to 10 mm over most of the region. Strain energy with moment magnitude equivalent to an M7 earthquake was released along this “megadetachment,” primarily between 2000.0 and 2005.5. Slip initiated in late 1998 to mid-1999 in northeastern Nevada and is best expressed in late 2003 during a magma injection event at Moho depth beneath the Sierra Nevada, accompanied by more rapid eastward relative displacement across the entire region. The event ended in the east at 2004.0 and in the remainder of the network at about 2005.5. Strain energy thus appears to have been transmitted from the Cordilleran interior toward the plate boundary, from high gravitational potential to low, via yielding on the megadetachment. The size and kinematic function of the proposed structure, in light of various proxies for lithospheric thickness, imply that the subcrustal lithosphere beneath Nevada is a strong, thin plate, even though it resides in a high heat flow tectonic regime. A strong lowermost crust and upper mantle is consistent with patterns of postseismic relaxation in the southern Great Basin, deformation microstructures and low water content in dunite xenoliths in young lavas in central Nevada, and high-temperature microstructures in analog surface exposures of deformed lower crust. Large-scale decoupling between crust and upper mantle is consistent with the broad distribution of strain in the upper crust versus the more localized distribution in the subcrustal lithosphere, as inferred by such proxies as low P wave velocity and mafic magmatism

Behaviour and Physiology: The Thermal Strategy of Leatherback Turtles

Background: Adult leatherback turtles (Dermochelys coriacea) exhibit thermal gradients between their bodies and the environment of $8uC in sub-polar waters and #4uC in the tropics. There has been no direct evidence for thermoregulation in leatherbacks although modelling and morphological studies have given an indication of how thermoregulation may be achieved. Methodology/Principal Findings: We show for the first time that leatherbacks are indeed capable of thermoregulation from studies on juvenile leatherbacks of 16 and 37 kg. In cold water (, 25uC), flipper stroke frequency increased, heat loss through the plastron, carapace and flippers was minimized, and a positive thermal gradient of up to 2.3uC was maintained between body and environment. In warm water (25 – 31uC), turtles were inactive and heat loss through their plastron, carapace and flippers increased. The thermal gradient was minimized (0.5uC). Using a scaling model, we estimate that a 300 kg adult leatherback is able to maintain a maximum thermal gradient of 18.2uC in cold sub-polar waters. Conclusions/Significance: In juvenile leatherbacks, heat gain is controlled behaviourally by increasing activity while heat flux is regulated physiologically, presumably by regulation of blood flow distribution. Hence, harnessing physiology and behaviour allows leatherbacks to keep warm while foraging in cold sub-polar waters and to prevent overheating in

Rapid induction of autoantibodies during ARDS and septic shock

<p>Abstract</p> <p>Background</p> <p>Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.</p> <p>Methods</p> <p>Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.</p> <p>Results</p> <p>From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.</p> <p>Conclusion</p> <p>The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.</p

Asymmetric Bidirectional Transcription from the FSHD-Causing D4Z4 Array Modulates DUX4 Production

Facioscapulohumeral Disease (FSHD) is a dominantly inherited progressive myopathy associated with aberrant production of the transcription factor, Double Homeobox Protein 4 (DUX4). The expression of DUX4 depends on an open chromatin conformation of the D4Z4 macrosatellite array and a specific haplotype on chromosome 4. Even when these requirements are met, DUX4 transcripts and protein are only detectable in a subset of cells indicating that additional constraints govern DUX4 production. Since the direction of transcription, along with the production of non-coding antisense transcripts is an important regulatory feature of other macrosatellite repeats, we developed constructs that contain the non-coding region of a single D4Z4 unit flanked by genes that report transcriptional activity in the sense and antisense directions. We found that D4Z4 contains two promoters that initiate sense and antisense transcription within the array, and that antisense transcription predominates. Transcriptional start sites for the antisense transcripts, as well as D4Z4 regions that regulate the balance of sense and antisense transcripts were identified. We show that the choice of transcriptional direction is reversible but not mutually exclusive, since sense and antisense reporter activity was often present in the same cell and simultaneously upregulated during myotube formation. Similarly, levels of endogenous sense and antisense D4Z4 transcripts were upregulated in FSHD myotubes. These studies offer insight into the autonomous distribution of muscle weakness that is characteristic of FSHD