Information, Learning, and Drug Diffusion: the Case of Cox-2 Inhibitors

The recent withdrawal of Cox-2 Inhibitors has generated debate on the role of information in drug diffusion: can the market learn the efficacy of new drugs, or does it depend solely on manufacturer advertising and FDA updates? In this study, we use a novel data set to study the diffusion of three Cox-2 Inhibitors ? Celebrex, Vioxx and Bextra ? before the Vioxx withdrawal. Our study has two unique features: first, we observe each patient?s reported satisfaction after consuming a drug. This patient level data set, together with market level data on FDA updates, media coverage, academic articles, and pharmaceutical advertising, allows us to model individual prescription decisions. Second, we distinguish across-patient learning of a drug?s general efficacy from the within-patient learning of the match between a drug and a patient. Our results suggest that prescription choice is sensitive to many sources of information. At the beginning of 2001 and upon Bextra entry in January 2002, doctors held a strong prior belief about the efficacy of Celebrex, Vioxx, and Bextra. As a result, the learning from patient satisfaction is gradual and more concentrated on drug-patient match than on across-patient spillovers. News articles are weakly beneficial for Cox-2 drug sales, but academic articles appear to be detrimental. The impact of FDA updates is close to zero once we control for academic articles, which suggests that FDA updates follow academic articles and therefore deliver little new information to doctors. We find that drug advertising also influences the choice of a patient?s medication. A number of counterfactual experiments are carried out to quantify the influence of information on market shares.

Accurate, Very Low Computational Complexity Spike Sorting Using Unsupervised Matched Subspace Learning

This paper presents an adaptable dictionary-based feature extraction approach for spike sorting offering high accuracy and low computational complexity for implantable applications. It extracts and learns identifiable features from evolving subspaces through matched unsupervised subspace filtering. To provide compatibility with the strict constraints in implantable devices such as the chip area and power budget, the dictionary contains arrays of {-1, 0 and 1} and the algorithm need only process addition and subtraction operations. Three types of such dictionary were considered. To quantify and compare the performance of the resulting three feature extractors with existing systems, a neural signal simulator based on several different libraries was developed. For noise levels $\sigma_N$ between 0.05 and 0.3 and groups of 3 to 6 clusters, all three feature extractors provide robust high performance with average classification errors of less than 8% over five iterations, each consisting of 100 generated data segments. To our knowledge, the proposed adaptive feature extractors are the first able to classify reliably 6 clusters for implantable applications. An ASIC implementation of the best performing dictionary-based feature extractor was synthesized in a 65-nm CMOS process. It occupies an area of 0.09 mm2 and dissipates up to about 10.48 μW from a 1 V supply voltage, when operating with 8-bit resolution at 30 kHz operating frequency

Thermal stability and durability of solar salt-based nanofluids inconcentrated solar power thermal energy storage: An approach from theeffect of diverse metal alloys corrosion

Concentrated Solar Power (CSP) technology has witnessed substantial growth, with forecasts predicting an increase of 3.4 GW between 2019 and 2024. This expansion necessitates the installation of energy storage systems to meet the growing demand. Solar molten salts, specifically a mixture of 60 % NaNO3 and 40 % KNO3, have emerged as the primary thermal energy storage (TES) medium in commercial CSP plants. However, a significant challenge lies in the corrosive nature of molten salt at high temperatures, which poses limitations in TES applications. The literature has explored a promising solution: reducing corrosion rates by incorporating nanoparticles into molten salts, creating nanofluids. To assess the viability of nanofluids for CSP, it is essential to understand how they perform under working conditions, especially regarding their thermal stability and durability. This study presents further evidence of nanofluid interactions with component materials under static working conditions. Specifically, focus on the impact of corrosion products precipitated during corrosion tests on the physical and thermal properties of Solar Salt-based silica dioxide nanofluids. In this research, nanofluids in contact with stainless steel, nickel‑chromium alloy, and carbon steel were examined before and after subjecting them to a 90-day thermal exposure at 500 °C. These findings provide valuable data on key thermo-physical properties during service, contributing to the design of more precise TES systems and enhancing their overall efficiency and effectiveness

Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases.

Autophagy is a major, conserved cellular pathway by which cells deliver cytoplasmic contents to lysosomes for degradation. Genetic studies have revealed extensive links between autophagy and neurodegenerative disease, and disruptions to autophagy may contribute to pathology in some cases. Autophagy degrades many of the toxic, aggregate-prone proteins responsible for such diseases, including mutant huntingtin (mHTT), alpha-synuclein (α-syn), tau, and others, raising the possibility that autophagy upregulation may help to reduce levels of toxic protein species, and thereby alleviate disease. This review examines autophagy induction as a potential therapy in several neurodegenerative diseases-Alzheimer's disease, Parkinson's disease, polyglutamine diseases, and amyotrophic lateral sclerosis (ALS). Evidence in cells and in vivo demonstrates promising results in many disease models, in which autophagy upregulation is able to reduce the levels of toxic proteins, ameliorate signs of disease, and delay disease progression. However, the effective therapeutic use of autophagy induction requires detailed knowledge of how the disease affects the autophagy-lysosome pathway, as activating autophagy when the pathway cannot go to completion (e.g., when lysosomal degradation is impaired) may instead exacerbate disease in some cases. Investigating the interactions between autophagy and disease pathogenesis is thus a critical area for further research

Presbyopia:Effectiveness of correction strategies

Presbyopia is a global problem affecting over a billion people worldwide. The prevalence of unmanaged presbyopia is as high as 50% of those over 50 years of age in developing world populations due to a lack of awareness and accessibility to affordable treatment, and is even as high as 34% in developed countries. Definitions of presbyopia are inconsistent and varied, so we propose a redefinition that states “presbyopia occurs when the physiologically normal age-related reduction in the eye's focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual's requirements”. Presbyopia is inevitable if one lives long enough, but intrinsic and extrinsic risk factors including cigarette smoking, pregnancy history, hyperopic or astigmatic refractive error, ultraviolet radiation, female sex (although accommodation is similar to males), hotter climates and some medical conditions such as diabetes can accelerate the onset of presbyopic symptoms. Whilst clinicians can ameliorate the symptoms of presbyopia with near vision spectacle correction, bifocal and progressive spectacle lenses, monovision, translating or multifocal contact lenses, monovision, extended depth of focus, multifocal (refractive, diffractive and asymmetric designs) or ‘accommodating’ intraocular lenses, corneal inlays, scleral expansion, laser refractive surgery (corneal monovision, corneal shrinkage, corneal multifocal profiles and lenticular softening), pharmacologic agents, and electro-stimulation of the ciliary muscle, none fully overcome presbyopia in all patients. While the restoration of natural accommodation or an equivalent remains elusive, guidance is gives on presbyopic correction evaluation techniques

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Bayesian analysis of random coefficient logit models using aggregate data

We present a Bayesian approach for analyzing aggregate level sales data in a market with differentiated products. We consider the aggregate share model proposed by Berry et al. [Berry, Steven, Levinsohn, James, Pakes, Ariel, 1995. Automobile prices in market equilibrium. Econometrica. 63 (4), 841-890], which introduces a common demand shock into an aggregated random coefficient logit model. A full likelihood approach is possible with a specification of the distribution of the common demand shock. We introduce a reparameterization of the covariance matrix to improve the performance of the random walk Metropolis for covariance parameters. We illustrate the usefulness of our approach with both actual and simulated data. Sampling experiments show that our approach performs well relative to the GMM estimator even in the presence of a mis-specified shock distribution. We view our approach as useful for those who are willing to trade off one additional distributional assumption for increased efficiency in estimation.Random coefficient logit Aggregate share models Bayesian analysis