Rhabdomyolysis in an HIV cohort: epidemiology, causes and outcomes.

BackgroundThe Literature on rhabdomyolysis in the HIV-positive population is sparse and limited. We aimed to explore the incidence, patient characteristics, etiologies and outcomes of rhabdomyolysis in a cohort of HIV-positive patients identified through the Johns Hopkins HIV clinical registry between June 1992 and April 2014.MethodsA retrospective analysis of 362 HIV-positive patients with non-cardiac CK elevation ≥1000 IU/L was performed. Both inpatients and outpatients were included. Incidence rate and potential etiologies for rhabdomyolysis were ascertained. The development of acute kidney injury (AKI, defined as doubling of serum creatinine), need for dialysis, and death in the setting of rhabdomyolysis were determined. Logistic regression was used to evaluate the association of peak CK level with the development of AKI.ResultsThree hundred sixty two cases of rhabdomyolysis were identified in a cohort of 7079 patients with a 38,382 person years follow-up time. The incidence rate was nine cases per 1000 person-years (95% CI: 8.5-10.5). Infection was the most common etiology followed by compression injury and drug/alcohol use. One-third of cases had multiple potential etiologies. AKI developed in 46% of cases; 20% of which required dialysis. Thirteen percent died during follow-up. After adjustment, AKI was associated with higher CK (OR 2.05 for each 1-log increase in CK [95% CI: 1.40-2.99]), infection (OR 5.48 [95% CI 2.65-11.31]) and higher HIV viral load (OR 1.22 per 1-log increase [95% CI: 1.03-1.45]).ConclusionRhabdomyolysis in the HIV-positive population has many possible causes and is frequently multifactorial. HIV-positive individuals with rhabdomyolysis have a high risk of AKI and mortality

Adaptive Controller Effects on Pilot Behavior

Adaptive control provides robustness and resilience for highly uncertain, and potentially unpredictable, flight dynamics characteristic. Some of the recent flight experiences of pilot-in-the-loop with an adaptive controller have exhibited unpredicted interactions. In retrospect, this is not surprising once it is realized that there are now two adaptive controllers interacting, the software adaptive control system and the pilot. An experiment was conducted to categorize these interactions on the pilot with an adaptive controller during control surface failures. One of the objectives of this experiment was to determine how the adaptation time of the controller affects pilots. The pitch and roll errors, and stick input increased for increasing adaptation time and during the segment when the adaptive controller was adapting. Not surprisingly, altitude, cross track and angle deviations, and vertical velocity also increase during the failure and then slowly return to pre-failure levels. Subjects may change their behavior even as an adaptive controller is adapting with additional stick inputs. Therefore, the adaptive controller should adapt as fast as possible to minimize flight track errors. This will minimize undesirable interactions between the pilot and the adaptive controller and maintain maneuvering precision

The Luminosity of SN 1999by in NGC 2841 and the Nature of `Peculiar' Type Ia Supernovae

We present UBVRIJHK photometry and optical spectroscopy of the so-called 'peculiar' Type Ia supernova 1999by in NGC 2841. The observations began one week before visual maximum light which is well-defined by daily observations. The light curves and spectra are similar to those of the prototypical subluminous event SN 1991bg. We find that maximum light in B occurred on 1999 May 10.3 UT (JD 2,451,308.8 +/- 0.3) with B=13.66 +/- 0.02 mag and a color of B_max-V_max=0.51 +/- 0.03 mag. The late-time color implies minimal dust extinction from the host galaxy. Our photometry, when combined with the recent Cepheid distance to NGC 2841 (Macri et al. 2001), gives a peak absolute magnitude of M_B=-17.15 +/- 0.23 mag, making SN 1999by one of the least luminous Type Ia events ever observed. We estimate a decline rate parameter of dm15(B)=1.90 mag, versus 1.93 for SN 1991bg, where 1.10 is typical for so-called 'normal' events. We compare SN 1999by with other subluminous events and find that the B_max-V_max color correlates strongly with the decline rate and may be a more sensitive indicator of luminosity than the fading rate for these objects. We find a good correlation between luminosity and the depth of the spectral feature at 580 nm, which had been attributed solely to Si II. We show that in cooler photospheres the 580 nm feature is dominated by Ti II, which provides a simple physical explanation for the correlation. Using only subluminous Type Ia supernovae we derive a Hubble parameter of H_0=75 +12 -11 km/s Mpc, consistent with values found from brighter events.Comment: 36 preprint pages including 18 figures. Near-IR photometry of the SN has been added to the paper. Scheduled to appear in ApJ vol. 613 (September 2004). High-resolution version available from http://www.nd.edu/~pgarnavi/sn99by/sn99by.p

Diverse viral glycoproteins as well as CD4 co-package into the same human immunodeficiency virus (HIV-1) particles

BACKGROUND: Retroviruses can acquire not only their own glycoproteins as they bud from the cellular membrane, but also some cellular and foreign viral glycoproteins. Many of these non-native glycoproteins are actively recruited to budding virions, particularly other viral glycoproteins. This observation suggests that there may be a conserved mechanism underlying the recruitment of glycoproteins into viruses. If a conserved mechanism is used, diverse glycoproteins should localize to a single budding retroviral particle. On the other hand, if viral glycoproteins have divergent mechanisms for recruitment, the different glycoproteins could segregate into different particles. RESULTS: To determine if co-packaging occurs among different glycoproteins, we designed an assay that combines virion antibody capture and a determination of infectivity based on a luciferase reporter. Virions were bound to a plate with an antibody against one glycoprotein, and then the infectivity was measured with cells that allow entry only with a second glycoprotein. We tested pairings of glycoproteins from HIV, murine leukemia virus (MLV), Rous sarcoma virus (RSV), vesicular stomatitis virus (VSV), and Ebola virus. The results showed that glycoproteins that were actively recruited into virions were co-packaged efficiently with each other. We also tested cellular proteins and found CD4 also had a similar correlation between active recruitment and efficient co-packaging, but other cellular proteins did not. CONCLUSION: Glycoproteins that are actively incorporated into HIV-1 virions are efficiently co-packaged into the same virus particles, suggesting that the same general mechanism for recruitment may act in many viruses

Inferring Foliar Water Uptake Using Stable Isotopes of Water

A growing number of studies have described the direct absorption of water into leaves, a phenomenon known as foliar water uptake. The resultant increase in the amount of water in the leaf can be important for plant function. Exposing leaves to isotopically enriched or depleted water sources has become a common method for establishing whether or not a plant is capable of carrying out foliar water uptake. However, a careful inspection of our understanding of the fluxes of water isotopes between leaves and the atmosphere under high humidity conditions shows that there can clearly be isotopic exchange between the two pools even in the absence of a change in the mass of water in the leaf. We provide experimental evidence that while leaf water isotope ratios may change following exposure to a fog event using water with a depleted oxygen isotope ratio, leaf mass only changes when leaves are experiencing a water deficit that creates a driving gradient for the uptake of water by the leaf. Studies that rely on stable isotopes of water as a means of studying plant water use, particularly with respect to foliar water uptake, must consider the effects of these isotopic exchange processes

A Spitzer c2d Legacy Survey to Identify and Characterize Disks with Inner Dust Holes

Understanding how disks dissipate is essential to studies of planet formation. However, identifying exactly how dust and gas dissipates is complicated due to difficulty in finding objects clearly in the transition of losing their surrounding material. We use Spitzer IRS spectra to examine 35 photometrically-selected candidate cold disks (disks with large inner dust holes). The infrared spectra are supplemented with optical spectra to determine stellar and accretion properties and 1.3mm photometry to measure disk masses. Based on detailed SED modeling, we identify 15 new cold disks. The remaining 20 objects have IRS spectra that are consistent with disks without holes, disks that are observed close to edge-on, or stars with background emission. Based on these results, we determine reliable criteria for identifying disks with inner holes from Spitzer photometry and examine criteria already in the literature. Applying these criteria to the c2d surveyed star-forming regions gives a frequency of such objects of at least 4% and most likely of order 12% of the YSO population identified by Spitzer. We also examine the properties of these new cold disks in combination with cold disks from the literature. Hole sizes in this sample are generally smaller than for previously discovered disks and reflect a distribution in better agreement with exoplanet orbit radii. We find correlations between hole size and both disk and stellar masses. Silicate features, including crystalline features, are present in the overwhelming majority of the sample although 10 micron feature strength above the continuum declines for holes with radii larger than ~7 AU. In contrast, PAHs are only detected in 2 out of 15 sources. Only a quarter of the cold disk sample shows no signs of accretion, making it unlikely that photoevaporation is the dominant hole forming process in most cases.Comment: 24 pages, 18 figures and 8 tables. Fixed a typo in Table

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry

IMPORTANCE: Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. OBJECTIVE: To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS2 score and the CHA2DS2-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. MAIN OUTCOMES AND MEASURES: The primary outcome was prescription of an OAC with warfarin sodium or a non-vitamin K antagonist OAC. RESULTS: The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS2 score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172; P < .001) and the CHA2DS2-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169; P < .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4. CONCLUSIONS AND RELEVANCE: In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription

A recombinant herpesviral vector containing a near-full-length SIVmac239 genome produces SIV particles and elicits immune responses to all nine SIV gene products

The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme. Three variations were constructed to drive expression of the SIV proteins: one with SIV\u27s own promoter region, one with a cytomegalovirus (cmv) immediate-early promoter/enhancer region, and one with an RRV dual promoter (p26 plus PAN). Following infection of rhesus fibroblasts in culture with these rRRV vectors, synthesis of the early protein Nef and the late structural proteins Gag and Env could be demonstrated. Expression levels of the SIV proteins were highest with the rRRV-SIVcmv-nfl construct. Electron microscopic examination of rhesus fibroblasts infected with rRRV-SIVcmv-nfl revealed numerous budding and mature SIV particles and these infected cells released impressive levels of p27 Gag protein ( \u3e 150 ng/ml) into the cell-free supernatant. The released SIV particles were shown to be incompetent for replication. Monkeys inoculated with rRRV-SIVcmv-nfl became persistently infected, made readily-detectable antibodies against SIV, and developed T-cell responses against all nine SIV gene products. Thus, rRRV expressing a near-full-length SIV genome mimics live-attenuated strains of SIV in several important respects: the infection is persistent; \u3e 95% of the SIV proteome is naturally expressed; SIV particles are formed; and CD8+ T-cell responses are maintained indefinitely in an effector-differentiated state. Although the magnitude of anti-SIV immune responses in monkeys infected with rRRV-SIVcmv-nfl falls short of what is seen with live-attenuated SIV infection, further experimentation seems warranted

Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization

While changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumour DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumour. Matched tumour, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select epithelial cells from normal tissue, and neoplastic cells from tumour for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal and tumour (63,271 CpG loci q \u3c 0.01), than between ipsilateral-normal and tumour (38,346 CpG loci q \u3c 0.01). We identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p \u3c 0.01). In this comparison, hypomethylated loci were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3 and hypermethylated loci were significantly enriched for CpG island shore regions. In addition, progression of shore hypermethylation was observed in tumours compared to matched ipsilateral normal tissue, and these alterations tracked to several well-established tumour suppressor genes. Our results indicate an epigenetic field effect in surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk