Changes in PM2.5 Peat Combustion Source Profiles with Atmospheric Aging in an Oxidation Flow Reactor

Smoke from laboratory chamber burning of peat fuels from Russia, Siberia, the USA (Alaska and Florida), and Malaysia representing boreal, temperate, subtropical, and tropical regions was sampled before and after passing through a potential-aerosol-mass oxidation flow reactor (PAM-OFR) to simulate intermediately aged (∼2 d) and well-aged (∼7 d) source profiles. Species abundances in PM2.5 between aged and fresh profiles varied by several orders of magnitude with two distinguishable clusters, centered around 0.1 % for reactive and ionic species and centered around 10 % for carbon. Organic carbon (OC) accounted for 58 %–85 % of PM2.5 mass in fresh profiles with low elemental carbon (EC) abundances (0.67 %–4.4 %). OC abundances decreased by 20 %–33 % for well-aged profiles, with reductions of 3 %–14 % for the volatile OC fractions (e.g., OC1 and OC2, thermally evolved at 140 and 280 ∘C). Ratios of organic matter (OM) to OC abundances increased by 12 %–19 % from intermediately aged to well-aged smoke. Ratios of ammonia (NH3) to PM2.5 decreased after intermediate aging. Well-aged NH+4 and NO−3 abundances increased to 7 %–8 % of PM2.5 mass, associated with decreases in NH3, low-temperature OC, and levoglucosan abundances for Siberia, Alaska, and Everglades (Florida) peats. Elevated levoglucosan was found for Russian peats, accounting for 35 %–39 % and 20 %–25 % of PM2.5 mass for fresh and aged profiles, respectively. The water-soluble organic carbon (WSOC) fractions of PM2.5 were over 2-fold higher in fresh Russian peat (37.0±2.7 %) than in Malaysian (14.6±0.9 %) peat. While Russian peat OC emissions were largely water-soluble, Malaysian peat emissions were mostly water-insoluble, with WSOC ∕ OC ratios of 0.59–0.71 and 0.18–0.40, respectively. This study shows significant differences between fresh and aged peat combustion profiles among the four biomes that can be used to establish speciated emission inventories for atmospheric modeling and receptor model source apportionment. A sufficient aging time (∼7 d) is needed to allow gas-to-particle partitioning of semi-volatilized species, gas-phase oxidation, and particle volatilization to achieve representative source profiles for regional-scale source apportionment

Bisphosphonate's and Intermittent Parathyroid Hormone's Effect on Human Spinal Fusion: A Systematic Review of the Literature.

There has been a conscious effort to address osteoporosis in the aging population. As bisphosphonate and intermittent parathyroid hormone (PTH) therapy become more widely prescribed to treat osteoporosis, it is important to understand their effects on other physiologic processes, particularly the impact on spinal fusion. Despite early animal model studies and more recent clinical studies, the impact of these medications on spinal fusion is not fully understood. Previous animal studies suggest that bisphosphonate therapy resulted in inhibition of fusion mass with impeded maturity and an unknown effect on biomechanical strength. Prior animal studies demonstrate an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. The purpose of this study was to determine if bisphosphonates and intermittent PTH treatment have impact on human spinal fusion. A systematic review of the literature published between 1980 and 2015 was conducted using major electronic databases. Studies reporting outcomes of human subjects undergoing 1, 2, or 3-level spinal fusion while receiving bisphosphonates and/or intermittent PTH treatment were included. The results of relevant human studies were analyzed for consensus on the effects of these medications in regards to spinal fusion. There were nine human studies evaluating the impact of these medications on spinal fusion. Improved fusion rates were noted in patients receiving bisphosphonates compared to control groups, and greater fusion rates in patients receiving PTH compared to control groups. Prior studies involving animal models found an improved fusion rate and fusion mass microstructure with the use of intermittent PTH. No significant complications were demonstrated in any study included in the analysis. Bisphosphonate use in humans may not be a deterrent to spinal fusion. Intermittent parathyroid use has shown early promise to increase fusion mass in both animal and human studies but further studies are needed to support routine use

The aging male: investigation, treatment and monitoring of late-onset hypogonadism in males

Androgen deficiency in the aging male has become a topic of increasing interest and debate throughout the world. The demographics clearly demonstrate the increasing percentage of the population that is in the older age groups. The data also support the concept that testosterone falls progressively with age and that a significant percentage of men over the age of 60 years have serum testosterone levels that are below the lower limits of young adults (age 20-30 years) men. The principal questions raised by these observations are whether older hypogonadal men will benefit from testosterone treatment and what will be the risks associated with such intervention. The past decade has brought evidence of benefit of androgen treatment on multiple target organs of hypogonadal men and recent studies show short-term beneficial effects of testosterone in older men that are similar to those in younger men. Long-term data on the effects of testosterone treatment in the older population are limited and specific risk data on the prostate and cardiovascular systems are needed. Answers to key questions of functional benefits that may retard frailty of the elderly are not yet available. The recommendations described below were prepared for the International Society of Andrology (ISA) and the International Society for the Study of the Aging Male (ISSAM) following a panel discussion with active participation from the audience sponsored by the ISA on the topic at the 4th ISSAM Congress in Prague in February 2004.peer-reviewe

Two-period linear mixed effects models to analyze clinical trials with run-in data when the primary outcome is continuous: Applications to Alzheimer\u27s disease.

Introduction: Study outcomes can be measured repeatedly based on the clinical trial protocol before randomization during what is known as the run-in period. However, it has not been established how best to incorporate run-in data into the primary analysis of the trial. Methods: We proposed two-period (run-in period and randomization period) linear mixed effects models to simultaneously model the run-in data and the postrandomization data. Results: Compared with the traditional models, the two-period linear mixed effects models can increase the power up to 15% and yield similar power for both unequal randomization and equal randomization. Discussion: Given that analysis of run-in data using the two-period linear mixed effects models allows more participants (unequal randomization) to be on the active treatment with similar power to that of the equal-randomization trials, it may reduce the dropout by assigning more participants to the active treatment and thus improve the efficiency of AD clinical trials

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Probing Proteinase Active Sites Using Oriented Peptide Mixture Libraries – ADAM-10

Oriented Peptide Mixture Libraries can provide a full matrix of preferred and disfavored amino acids at each subsite of an optimal substrate for a new proteinase. This approach is rapid and convenient, requiring only two mixture libraries to complete the analysis. In this paper we demonstrate an extension of this type of analysis, using a focused library employing unnatural amino acids to probe the depth of the S1 position in the catalytic site of the alpha secretase ADAM-10. This analysis indicates that ADAM- 10 will accept amino acids with substantial length and hydrophobicity (e.g. 2- naphthylalanine), but suggests that the S1 site has limitations in the apparent “width” of substituents being presented (e.g. 1-naphthylalanine; gamma branching). A highly selective and efficient substrate for ADAM-10, with a selectivity factor of 380,000 M-1 s -1 , was derived from the predicted consensus substrate. This detailed analysis provides a starting point for the design of inhibitors of this interesting proteinase