Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy

Background: Clinical deterioration after initiation of antiretroviral therapy may result from restored immunity. There is no standard clinical definition for immune reconstitution syndrome. The objectives of this study were to validate a proposed definition and to identify factors predictive of immune reconstitution syndrome. Methods: This was a retrospective case-control study from an academic university medical practice. Cases were matched to ⩾2 control subjects by CD4+ cell count at the time of initiation of antiretroviral therapy. Cases and “mock cases” were blindly reviewed by 2 human immunodeficiency virus (HIV) experts. Results: Twenty possible cases of immune reconstitution syndrome were identified; HIV experts excluded all cases of herpes zoster (shingles), with agreement on real and mock cases of 92%. For 14 confirmed case patients (compared with 40 control subjects), immune reconstitution syndrome was associated with a higher number of prior opportunistic infections (P = .003) and higher CD8+ cell counts at baseline (P = .05) and at week 12 (P = .02). Immune reconstitution syndrome was associated with lower baseline levels of alanine aminotransferase (P = .05) and hemoglobin (P = .02). On multivariate analysis, the number of prior opportunistic infections (odds ratio, 2.7; P = .007) and lower hemoglobin level at baseline (odds ratio, 0.8; P = .003) were independently associated with development of immune reconstitution syndrome. A predictive model was defined by classification and regression tree analysis with a sensitivity and specificity of 78.57% and 87.50%, respectively, for an importance score of ⩾4 (on a scale of 0.0 to 100.0), and 92.86% and 80.00%, respectively, for a score of ⩾2, using the number of prior opportunistic infections, CD8+ cell count, and hemoglobin level. Conclusions: A standard definition for immune reconstitution syndrome is possible. Patients with a greater severity of illness at initiation of antiretroviral therapy are at risk for immune reconstitution syndrome. The model defined by classification and regression tree analysis may provide a basis for risk stratification before initiation of antiretroviral therapy

Frequency control of photonic crystal membrane resonators by mono-layer deposition

We study the response of GaAs photonic crystal membrane resonators to thin film deposition. Slow spectral shifts of the cavity mode of several nanometers are observed at low temperatures, caused by cryo-gettering of background molecules. Heating the membrane resets the drift and shielding will prevent drift altogether. In order to explore the drift as a tool to detect surface layers, or to intentionally shift the cavity resonance frequency, we studied the effect of self-assembled monolayers of polypeptide molecules attached to the membranes. The 2 nm thick monolayers lead to a discrete step in the resonance frequency and partially passivate the surface.Comment: 3 pages, 4 figures, submitted to Appl. Phys. Let

DNA methylation changes from primary cultures through senescence-bypass in Syrian hamster fetal cells initially exposed to benzo[a]pyrene

Current chemical testing strategies are limited in their ability to detect non-genotoxic carcinogens (NGTxC). Epigenetic anomalies develop during carcinogenesis regardless of whether the molecular initiating event is associated with genotoxic (GTxC) or NGTxC events; therefore, epigenetic markers may be harnessed to develop new approach methodologies that improve the detection of both types of carcinogens. This study used Syrian hamster fetal cells to establish the chronology of carcinogen-induced DNA methylation changes from primary cells until senescence-bypass as an essential carcinogenic step. Cells exposed to solvent control for 7 days were compared to naïve primary cultures, to cells exposed for 7 days to benzo[a]pyrene, and to cells at the subsequent transformation stages: normal colonies, morphologically transformed colonies, senescence, senescence-bypass, and sustained proliferation in vitro. DNA methylation changes identified by reduced representation bisulphite sequencing were minimal at day-7. Profound DNA methylation changes arose during cellular senescence and some of these early differentially methylated regions (DMRs) were preserved through the final sustained proliferation stage. A set of these DMRs (e.g., Pou4f1, Aifm3, B3galnt2, Bhlhe22, Gja8, Klf17, and L1l) were validated by pyrosequencing and their reproducibility was confirmed across multiple clones obtained from a different laboratory. These DNA methylation changes could serve as biomarkers to enhance objectivity and mechanistic understanding of cell transformation and could be used to predict senescence-bypass and chemical carcinogenicity

The narratives of Hardship: : The new and the old poor in the aftermath of the 2008 crisis in Europe

This document is the Accepted Manuscript version of the following article: Hulya Dagdeviren, Matthew Donoghue, and Lars Meier, ‘The narratives of hardship: the new and the old poor in the aftermath of the 2008 crisis in Europe’, The Sociological Review, vol. 65 (2): 369-385, May 2017. The final, definitive version of record is available online at doi: https://doi.org/10.1111/1467-954X.12403. Published by SAGE.This paper examines poverty and hardship in Europe after the 2008 crisis, using household interviews in nine European countries. A number of findings deserve highlighting. First, making a distinction between ‘the old poor’ (those who lived in poverty before as well as after the crisis) and ‘the new poor’ (thosewho fell into hardship after the crisis), we show that hardship is experienced quite differently by these groups. Second, the household narratives showed that while material deprivations constitute an important aspect of hardship, the themes of insecurity and dependency also emerged as fundamental dimensions. In contrast to popular political discourse in countries such as the UK, dependency on welfare or family was experienced as a source of distress and manifested as a form of hardship by participants in all countries covered in this study.Peer reviewedFinal Accepted Versio

Delayed Endovascular Coil Extrusion following Internal Carotid Artery Embolization

Internal carotid artery injury is a rare and devastating complication of endoscopic sinus and skull base surgery that has an associated mortality rate of 15%. This case describes a patient who developed massive epistaxis following routine sinus surgery and was eventually diagnosed with a pseudoaneurysm of the cavernous internal carotid artery. Endovascular coiling and Onyx (Covidien, Irvine, California, United States) liquid embolization were ultimately used to completely occlude the internal carotid artery with resolution of bleeding; however, the patient had an unexpected late complication of coil extrusion through the pseudoaneurysm sac into the sphenoid sinus and nasal cavity. The endoscopic skull base team safely excised the coils endoscopically without recurrent bleeding. We describe the multidisciplinary operative management of this case of endovascular coil extrusion to increase awareness of this potentially life-threatening complication

Imaging Carbon Monoxide Emission in the Starburst Galaxy NGC 6000

We present measurements of carbon monoxide emission in the central region of the nearby starburst NGC 6000 taken with the Submillimeter Array. The J=2-1 transition of 12CO, 13CO, and C18O were imaged at a resolution of ~3''x2'' (450x300 pc). We accurately determine the dynamical center of NGC 6000 at R.A(J2000.0)=15h49m49.5s and dec(J2000.0)=-29d23'13'' which agrees with the peak of molecular emission position. The observed CO dynamics could be explained in the context of the presence of a bar potential affecting the molecular material, likely responsible for the strong nuclear concentration where more than 85% of the gas is located. We detect a kinematically detached component of dense molecular gas at relatively high velocity which might be fueling the star formation. A total nuclear dynamical mass of 7x10^9 Msun is derived and a total mass of gas of 4.6x10^8 Msun, yielding a Mgas/Mdyn~6%, similar to other previously studied barred galaxies with central starbursts. We determined the mass of molecular gas with the optically thin isotopologue C18O and we estimate a CO-to-H2 conversion factor X(CO)=0.4x10^20 cm-2/(K km s-1) in agreement with that determined in other starburst galaxies.Comment: 31 pages, 7 figures. Accepted for publication in Astronomical Journal

Investigation of Combustion Control in a Dump Combustor Using the Feedback Free Fluidic Oscillator

A feedback free fluidic oscillator was designed and integrated into a single element rocket combustor with the goal of suppressing longitudinal combustion instabilities. The fluidic oscillator uses internal fluid dynamics to create an unsteady outlet jet at a specific frequency. An array of nine fluidic oscillators was tested to mimic modulated secondary oxidizer injection into the combustor dump plane. The combustor has a coaxial injector that uses gaseous methane and decomposed hydrogen peroxide with an overall O/F ratio of 11.7. A sonic choke plate on an actuator arm allows for continuous adjustment of the oxidizer post acoustics enabling the study of a variety of instability magnitudes. The fluidic oscillator unsteady outlet jet performance is compared against equivalent steady jet injection and a baseline design with no secondary oxidizer injection. At the most unstable operating conditions, the unsteady outlet jet saw a 67% reduction in the instability pressure oscillation magnitude when compared to the steady jet and baseline data. Additionally, computational fluid dynamics analysis of the combustor gives insight into the flow field interaction of the fluidic oscillators. The results indicate that open loop high frequency propellant modulation for combustion control can be achieved through fluidic devices that require no moving parts or electrical power to operate

Aging ebbs the flow of thought: Adult age differences in mind wandering, executive control, and self-evaluation

Abstract: Two experiments examined the relations among adult aging, mind wandering, and executive-task performance, following from surprising laboratory findings that older adults report fewer taskunrelated thoughts (TUTs) than do younger adults (e.g., aging | mind wandering | executive control | consciousness | working memory

Employing human rights frameworks to realize access to an HIV cure

IntroductionThe scale of the HIV pandemic – and the stigma, discrimination and violence that surrounded its sudden emergence – catalyzed a public health response that expanded human rights in principle and practice. In the absence of effective treatment, human rights activists initially sought to protect individuals at high risk of HIV infection. With advances in antiretroviral therapy, activists expanded their efforts under international law, advocating under the human right to health for individual access to treatment.DiscussionAs a clinical cure comes within reach, human rights obligations will continue to play a key role in political and programmatic decision-making. Building upon the evolving development and implementation of the human right to health in the global response to HIV, we outline a human rights research agenda to prepare for HIV cure access, investigating the role of human rights law in framing 1) resource allocation, 2) international obligations, 3) intellectual property and 4) freedom from coercion.ConclusionsThe right to health is widely recognized as central to governmental, intergovernmental and non-governmental responses to the pandemic and critical both to addressing vulnerability to infection and to ensuring universal access to HIV prevention, treatment, care and support. While the advent of an HIV cure will raise new obligations for policymakers in implementing the right to health, the resolution of past debates surrounding HIV prevention and treatment may inform claims for universal access