Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among Combination Antiretroviral Therapy-Treated Adults in Botswana: Results from a Clinical Trial

Nucleoside analogue reverse transcriptase inhibitors are an integral component of combination antiretroviral treatment regimens. However, their ability to inhibit polymerase-γ has been associated with several mitochondrial toxicities, including potentially life-threatening lactic acidosis. A total of 650 antiretroviral-naive adults (69% female) initiated combination antiretroviral therapy (cART) and were intensively screened for toxicities including lactic acidosis as part of a 3-year clinical trial in Botswana. Patients were categorized as no lactic acidosis symptoms, minor symptoms but lactate <4.4 mmol/liter, and symptoms with lactate ≥ 4.4 mmol/liter [moderate to severe symptomatic hyperlactatemia (SH) or lactic acidosis (LA)]. Of 650 participants 111 (17.1%) developed symptoms and/or laboratory results suggestive of lactic acidosis and had a serum lactate drawn; 97 (87.4%) of these were female. There were 20 events, 13 having SH and 7 with LA; all 20 (100%) were female (p<0.001). Cox proportional hazard analysis limited to the 451 females revealed that having a higher baseline BMI was predictive for the development of SH/LA [aHR=1.17 per one-unit increase (1.08-1.25), p<0.0001]. Ordered logistic regression performed among all 650 patients revealed that having a lower baseline hemoglobin [aOR=1.28 per one-unit decrease (1.1-1.49), p=0.002] and being randomized to d4T/3TC-based cART [aOR=1.76 relative to ZDV/3TC (1.03-3.01), p=0.04] were predictive of the symptoms and/or the development of SH/LA. cART-treated women in sub-Saharan Africa, especially those having higher body mass indices, should receive additional monitoring for SH/LA. Women presently receiving d4T/3TC-based cART in such settings also warrant more intensive monitoring

Revisions in Need of Revising: What Went Wrong in the Iraq War

Though critics have made a number of telling points against the Bush administration\u27s conduct of the Iraq war, the most serious problems facing Iraq and its American occupiers—criminal anarchy and lawlessness, a raging insurgency and a society divided into rival and antagonistic groups—were virtually inevitable consequences that flowed from the act of war itself. Military and civilian planners were culpable in failing to plan for certain tasks, but the most serious problems had no good solution. Even so, there are lessons to be learned. These include the danger that the imperatives of force protection may sacrifice the broader political mission of U.S. forces and the need for skepticism over the capacity of outsiders to develop the skill and expertise required to reconstruct decapitated states.https://press.armywarcollege.edu/monographs/1725/thumbnail.jp

“There is Just a Sense of Joy in This Work”: Drivers of Faculty Engagement with Community

American universities have been engaged with their communities as long as there have been universities in America. The nature, purpose, and motivation behind that engagement have evolved. This article explores the motivation behind faculty engagement with their communities. We wanted to better understand what compels faculty to participate in and work in the community despite the many and varied barriers that might stand in their way. We explored the why and how of participation with a significant emphasis on the why. This study builds on the work of Wade and Demb[i] and their Faculty Engagement Framework (FEM) described in this paper by answering their call for a “multi-dimensional, dynamic, and holistic description of the factors that affect faculty proclivities to value. . . engagement-related activities”.[ii] Through our qualitative research, we propose that faculty engage in their communities due to various personal and professional motivations, regardless of the institutional supports and practices that universities may provide. We found, however, that without supportive institutional structures in place, universities may not be able to sustain faculty engagement in their communities. [i] Amy Wade and Ada Demb. “A conceptual model to explore faculty community engagement.” Michigan Journal of Community Service Learning, 15, no. 2 (2009): 5-16. http://hdl.handle.net/2027/spo.3239521.0015.201. [ii] Wade and Demb. A conceptual model, 14

How many human proteoforms are there?

Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype

Investigation of Plasmon Resonance Tunneling through Subwavelength Hole Arrays in Highly Doped Conductive ZnO Films

Experimental results pertaining to plasmon resonance tunneling through a highly conductive zinc oxide (ZnO) layer with subwavelength hole-arrays is investigated in the mid-infrared regime. Gallium-doped ZnO layers are pulsed-laser deposited on a silicon wafer. The ZnO has metallic optical properties with a bulk plasma frequency of 214 THz, which is equivalent to a free space wavelength of 1.4 μm. Hole arrays with different periods and hole shapes are fabricated via a standard photolithography process. Resonant mode tunneling characteristics are experimentally studied for different incident angles and compared with surface plasmontheoretical calculations and finite-difference time-domain simulations. Transmission peaks, higher than the baseline predicted by diffraction theory, are observed in each of the samples at wavelengths that correspond to the excitation of surface plasmon modes

Biomass round bales infield aggregation logistics scenarios

Biomass bales often need to be aggregated (collected into groups and transported) to a field-edge stack or a temporary storage before utilization. Several logistics scenarios for aggregation involving equipment and aggregation strategies were modeled and evaluated. Cumulative Euclidean distance criteria evaluated the various aggregation scenarios. Application of a single-bale loader that aggregated bales individually was considered as the “control” scenario with which others were compared. A computer simulation program developed determined bale coordinates in ideal and random layouts that evaluated aggregation scenarios. Simulation results exhibited a “diamond pattern” of bales on ideal layout and a “random pattern” emerged when ≥ 10% variation was introduced. Statistical analysis revealed that the effect of field shape, swath width, biomass yield, and randomness on bale layout did not affect aggregation logistics, while area and number of bales handled had significant effects. Number of bales handled in the direct method significantly influenced the efficiency. Self-loading bale picker with minimum distance path (MDP, 80%) and parallel transport of loader and truck with MDP (78%) were ranked the highest, and single-bale central grouping the lowest (29%) among 19 methods studied. The MDP was found significantly more efficient (4%-16%) than the baler path. Simplistic methods, namely a direct triple-bale loader with MDP (64%-66%), or a loader and truck handling six bales running parallel with MDP (75%-82%) were highly efficient. Great savings on cumulative distances that directly influence time, fuel, and cost were realized when the number of bales handled was increased or additional equipment was utilized