Incidence and US Costs of Corticosteroid-Associated Adverse Events: A Systematic Literature Review

OBJECTIVE: The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. METHODS: A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. RESULTS: A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to $26,471.80 for nonfatal myocardial infarction, and per-event costs as high as$18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. CONCLUSION: Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers

FraudDroid: Automated Ad Fraud Detection for Android Apps

Although mobile ad frauds have been widespread, state-of-the-art approaches in the literature have mainly focused on detecting the so-called static placement frauds, where only a single UI state is involved and can be identified based on static information such as the size or location of ad views. Other types of fraud exist that involve multiple UI states and are performed dynamically while users interact with the app. Such dynamic interaction frauds, although now widely spread in apps, have not yet been explored nor addressed in the literature. In this work, we investigate a wide range of mobile ad frauds to provide a comprehensive taxonomy to the research community. We then propose, FraudDroid, a novel hybrid approach to detect ad frauds in mobile Android apps. FraudDroid analyses apps dynamically to build UI state transition graphs and collects their associated runtime network traffics, which are then leveraged to check against a set of heuristic-based rules for identifying ad fraudulent behaviours. We show empirically that FraudDroid detects ad frauds with a high precision (93%) and recall (92%). Experimental results further show that FraudDroid is capable of detecting ad frauds across the spectrum of fraud types. By analysing 12,000 ad-supported Android apps, FraudDroid identified 335 cases of fraud associated with 20 ad networks that are further confirmed to be true positive results and are shared with our fellow researchers to promote advanced ad fraud detectionComment: 12 pages, 10 figure

Health shocks and natural resource management: Evidence from Western Kenya

Poverty and altered planning horizons brought on by the HIV/AIDS epidemic can change individual discount rates, altering incentives to conserve natural resources. Using longitudinal household survey data from western Kenya, we estimate the effects of health status on investments in soil quality, as indicated by households’ agricultural land fallowing decisions. We first show that this effect is theoretically ambiguous: while health improvements lower discount rates and thus increase incentives to conserve natural resources, they also increase labor productivity and make it more likely that households can engage in labor-intensive resource extraction activities. We find that household size and composition are predictors of whether the effect of health improvements on discount rates dominates the productivity effect, or vice-versa. Since households with more and younger members are better able to reallocate labor to cope with productivity shocks, the discount rate effect dominates for these households and health improvements lead to greater levels of conservation. In smaller families with less substitutable labor, the productivity effect dominates and health improvements lead to greater environmental degradatio

Development of scalable manufacturing process and GMP-compatible formulation for a novel recombinant schistosomiasis vaccine

Schistosomiasis is a parasitic disease spread by fresh water snails. After malaria, schistosomiasis is the deadliest parasitic disease, plaguing an estimated 200 million people worldwide, and causing up to 280,000 fatalities in Africa. This neglected tropical disease has also emerged as an important co-factor in Africa’s HIV/AIDS epidemic, especially among women and adolescent girls. Together with hookworm disease and leishmaniasis, it ranks as the neglected tropical disease with the highest disease burden as defined by disability-adjusted life years (DALYs)1. Although treatments exist, such as praziquantel chemotherapy, a vaccine will likely be needed to prevent infection and re-infection, interrupt disease transmission, and ultimately establish long-term control and elimination of the disease. No such vaccine currently exists, but a promising candidate is currently under development at Texas Children’s Hospital Center for Vaccine Development (TCH-CVD). The Sm-TSP-2 schistosomiasis vaccine comprises a 9 kDa recombinant protein corresponding to the extracellular domain of a unique S. mansoni tetraspanin found in the parasite’s tegumental surface. Sm-TSP-2 was expressed as a recombinant protein secreted by the yeast PichiaPinkTM and purified in a two-step process, which resulted in a protein recovery yield of 31% and a protein purity of 97%.2 The developed processes were suitable for production of purified protein for subsequent formulation and Phase 1 clinical studies. However, improvements in process yield and efficiency, as well as transition of the formulation to GMP-compatible materials, are desirable for the advancement of this candidate through subsequent clinical phases and large-scale manufacturing. TCH-CVD and MilliporeSigma are conducting a collaborative project to optimize the efficiency and scalability of the Sm-STP-2 schistosomiasis vaccine manufacturing process. The overall goal of this work is to develop a safe and low-cost process for the purification of the vaccine antigen. This was accomplished by redesigning the original process, which utilized 750kD hollow fiber and 3kD cellulose membrane tangential flow filtration (TFF) devices for the clarification and concentration of the Pichia pastoris-based vaccine lysate process feed. The level of solids in the fermentation broth (30%) had required a dilution to enable processing through the hollow fiber device, which led to decreased product yield and increased complexity. MilliporeSigma assisted TCH-CVD with studies to eliminate the dilution prior to lysate clarification and to also streamline the process to enable Texas Children’s to simultaneously clarify and concentrate the yeast lysate. 0.1um, open-channel, stacked plate, membrane sheet TFF devices were successfully used to clarify the undiluted lysate. The TFF operating parameters (specifically the feed and permeate flow rates) were optimized to enable the downstream 3kD concentration process to run concurrently in a cascade TFF. Enhancement of the chromatography operations is currently underway as well. This presentation will detail the optimized clarification and concentration process and highlight the economic and process simplification benefits. Work was also performed to optimize the vaccine formulation. Extensive studies were previously conducted to identify excipients and conditions to maximize the stability of soluble recombinant Sm-TSP-2.3 Additional components were tested to find alternative GMP-grade reagents that maintained or improved the stability of the vaccine. REFRENCES 1. Forgotten People, Forgotten Diseases: The Neglected Tropical Diseases and Their Impact on Global Health and Development, Second Edition. Peter J. Hotez. American Society for Microbiology Press, Washington, DC, USA, 2013. 2. Curti E et al. Hum Vaccin Immunother. 2013 Nov;9(11):2342-50. 3. Cheng W et al. Hum Vaccin Immunother. 2013 Nov;9(11):2351-61

Epitaxially Driven Phase Selectivity of Sn in Hybrid Quantum Nanowires

Hybrid semiconductor-superconductor nanowires constitute a pervasive platform for studying gate-tunable superconductivity and the emergence of topological behavior. Their low dimensionality and crystal structure flexibility facilitate unique heterostructure growth and efficient material optimization, crucial prerequisites for accurately constructing complex multicomponent quantum materials. Here, we present an extensive study of Sn growth on InSb, InAsSb, and InAs nanowires and demonstrate how the crystal structure of the nanowires drives the formation of either semimetallic α-Sn or superconducting β-Sn. For InAs nanowires, we observe phase-pure superconducting β-Sn shells. However, for InSb and InAsSb nanowires, an initial epitaxial α-Sn phase evolves into a polycrystalline shell of coexisting α and β phases, where the β/α volume ratio increases with Sn shell thickness. Whether these nanowires exhibit superconductivity or not critically relies on the β-Sn content. Therefore, this work provides key insights into Sn phases on a variety of semiconductors with consequences for the yield of superconducting hybrids suitable for generating topological systems

Effect of Low-Passage Number on Dengue Consensus Genomes and Intra-host Variant Frequencies

Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low-passage number increases viral load, but few studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence and the intra-host virus population frequencies. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 posi- tive sera and their corresponding viral isolates (T. splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 500×, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNVs with frequencies ≥5% were often preserved between the samples, and that the number of iSNV positions, and sample diversity, at this frequency cutoff did not differ significantly between the sample pairs (clinical sample and isolate) in either DENV1 or DENV2 data. Our results show that low-passage DENV isolate consensus genomes are largely representative of their direct sample parental viruses, and that low-passage isolates often mirror high frequency within-host variants from direct samples

Taurine Administration Counteracts Aging-Associated Impingement of Skeletal Muscle Regeneration by Reducing Inflammation and Oxidative Stress

Abstract: Sarcopenia, which occurs during aging, is characterized by the gradual loss of skeletal muscle mass and function, resulting in a functional decline in physical abilities. Several factors contribute to the onset of sarcopenia, including reduced regenerative capacity, chronic low-grade inflammation, mitochondrial dysfunction, and increased oxidative stress, leading to the activation of catabolic pathways. Physical activity and adequate protein intake are considered effective strategies able to reduce the incidence and severity of sarcopenia by exerting beneficial effects in improving the muscular anabolic response during aging. Taurine is a non-essential amino acid that is highly expressed in mammalian tissues and, particularly, in skeletal muscle where it is involved in the regulation of biological processes and where it acts as an antioxidant and anti-inflammatory factor. Here, we evaluated whether taurine administration in old mice counteracts the physiopathological effects of aging in skeletal muscle. We showed that, in injured muscle, taurine enhances the regenerative process by downregulating the inflammatory response and preserving muscle fiber integrity. Moreover, taurine attenuates ROS production in aged muscles by maintaining a proper cellular redox balance, acting as an antioxidant molecule. Although further studies are needed to better elucidate the molecular mechanisms responsible for the beneficial effect of taurine on skeletal muscle homeostasis, these data demonstrate that taurine administration ameliorates the microenvironment allowing an efficient regenerative process and attenuation of the catabolic pathways related to the onset of sarcopenia