Miracle-dz/UniFAR-FTUs huggingface dataset:
Incentive formularies and changes in prescription drug spending.

OBJECTIVES To examine the impact of incentive formularies on prescription drug spending shifts in formulary compliance, use of generic medications, and mail-order fulfillment in the year after introduction of a new pharmacy benefit strategy. STUDY DESIGN Pre-post comparison study with matched concurrent control group (difference-indifferences analysis). METHODS Study subjects were continuously enrolled patients from a single large health plan in the northeastern United States. Health plan administrative data were used to determine the total, health plan, and out-of-pocket spending in the year before and the year after the introduction of 12 different benefit changes, including 1 in which copayments decreased. RESULTS Overall, changing from a single-tier or 2-tier formulary to a 3-tier formulary was associated with a decrease in total drug spending of about 5% to 15%. Plan spending decreased more dramatically, about 20%, whereas out-of-pocket spending that resulted from higher copayments increased between 20% and >100%. Changing to an incentive formulary with higher copayments was accompanied by a small but inconsistent decrease in use of nonformulary selections and a concomitant increase in both generic and formulary preferred utilization. Mail-order fulfillment doubled, albeit from a low baseline level. CONCLUSIONS Switching to incentive formulary arrangements with higher levels of copayments generally led to overall lower drug costs and vice versa. These effects varied with the degree of change, level of baseline spending, and magnitude of the copayments. Whether these effects are beneficial overall depends on potential health effects and spillover effects on medical spending.
A NON-NUMERIC APPROACH TO UNCERTAIN REASONING

This paper presents a non-numeric approach to uncertain reasoning by extending the incidence calculus. In parallel to the well known fuzzy, belief/plausibility, probability, and necessity/possibility measures, the corresponding classes of non-numeric functions are examined. A method of constructing non-numeric functions is discussed using the notion of compatibility relations. Non-numeric functions are used to interpret uncertain reasoning by providing possible-worlds semantics for both qualitative and quantitative methods.
Sleep Apnea Is Independently Associated With Peripheral Arterial Disease in the Hispanic Community Health Study/Study of Latinos

Objective— Sleep apnea (SA) has been linked with various forms of cardiovascular disease, but little is known about its association with peripheral artery disease (PAD) measured using the ankle–brachial index. This relationship was evaluated in the Hispanic Community Health Study/Study of Latinos. Approach and Results— We studied 8367 Hispanic Community Health Study/Study of Latinos participants who were 45 to 74 years of age. Sleep symptoms were examined with the self-reported Sleep Health Questionnaire. SA was assessed using an in-home sleep study. Systolic blood pressure was measured in all extremities to compute the ankle–brachial index. PAD was defined as ankle–brachial index <0.90 in either leg. Multivariable logistic regression was used to investigate the association between moderate-to-severe SA, defined as apnea–hypopnea index ≥15, and the presence of PAD. Analyses were adjusted for covariates. The prevalence of PAD was 4.7% (n=390). The mean apnea–hypopnea index was significantly higher among adults with PAD compared with those without (11.1 versus 8.6 events/h; P=0.046). After adjusting for covariates, moderate-to-severe SA was associated with a 70% increase in the odds of PAD (odds ratio, 1.7; 95% confidence interval, 1.1–2.5; P=0.0152). This association was not modified by sex (P=0.8739). However, there was evidence that the association between moderate-to-severe SA and PAD varied by Hispanic/Latino background (P<0.01). Specifically, the odds were stronger in Mexican (adjusted odds ratio, 2.9; 95% confidence interval, 1.3–6.2) and in Puerto Rican Americans (adjusted odds ratio, 2.0; 95% confidence interval, 0.97–4.2) than in other backgrounds. Conclusions— Moderate-to-severe SA is associated with higher odds of PAD in Hispanic/Latino adults.
Optimization of Ferment Condition of ε-Poly-L-Lysine by Response Surface Methodology

Streptomyces albus Y07, a strain which could produce ε-Poly-L-lysine (ε-PL) had been screened in our previous study. The fermentation conditions for ε-Poly-L-lysine production were further optimized through response surface method in this work. A central composite design was adopted to study the effect of culture volume, shaking speed, initial culture pH, as well as inoculation amount on ε-PL production. A quadratic polynomial equation for ε-Poly-L-lysine production was obtained by multiple regression analysis. The equation was as follow: The accuracy and general availability of the polynomial model were proved to be adequate with R2 Pre = 0.8373. The optimized conditions were as follows: culture volumn: 50/500ml, culture pH = 7, inoculation amount: 10% of the total culture volume, shaking speed: 180rpm. Under the optimized conditions, the ε-PL production reached 1.085g / L. And the validity of the predicited model was further confirmed through verification experiments.
Investigating the Role of Current Strength in tDCS Modulation of Working Memory Performance in Healthy Controls

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has the potential to improve working memory (WM) deficits in many clinical disorders. The aim of this study was to investigate the role of current strength on the ability of anodal tDCS to improve WM, and secondly to investigate the time course of effects. Twelve healthy participants underwent three stimulation sessions consisting of 20 min of either 1 mA anodal tDCS, 2 mA anodal tDCS, or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) localized via F3, all whilst completing a WM task. Intra-stimulation and post-stimulation WM performances were measured using the n-back and Sternberg tasks respectively. Results revealed no significant improvements in participants’ accuracy, but a significant interaction was found with respect to current strength and time for accurate reaction time. The finding provides partial support for the hypothesis, in that it appears current strength may affect aspects of WM performance. However, more research is needed, and a higher difficulty level of WM tasks is one of the suggestions discussed for future research.
Acute Kidney Injury Reduces Survival in Very Low Birth Weight Infants

Acute kidney injury (AKI) independently predicts mortality in children and adults. Our understanding of the epidemiology of AKI in very LBW (VLBW) infants is limited to retrospective studies. After adjustment for demographics, comorbidities, and interventions, infants with AKI have decreased survival compared with those without AKI. The study was conducted in regional quaternary care NICU of the University of Alabama at Birmingham. VLBW infants were followed prospectively and were classified into a serum creatinine (SCr)-based classification for AKI. Forty-one of 229 (18%) VLBW infants developed AKI. Those with AKI were more likely to have umbilical artery catheters, assisted ventilation, blood pressure medications, and lower 1- and 5-min Apgar scores. Of the infants with AKI, 17 of 41 (42%) died compared with 9 of 188 (5%) of those without AKI (p < 0.001). AKI was associated with mortality with a crude hazard ratio (HR) of 9.3 (95% CI, 4.1–21.0). After adjusting for potential confounders, those with AKI had higher chance of death as the adjusted HR was 2.4 (95% CI 0.95–6.04). AKI is associated with mortality in VLBW infants. Efforts to prevent and ameliorate the impact of AKI may improve the outcomes in this vulnerable population.
Factors influencing physician use of clinical electronic information technologies after adoption by their medical group practices

Background: A major factor limiting efficiency and quality gains from clinical information technologies is the lack of full use by the clinicians. Purpose: To identify the practice and physician characteristics that influence the use of e-scripts after adoption. Methods: Data were obtained from 27 primary care medical group practices that had e-script technology for 2 years. Physician and practice characteristics were obtained from the clinics, and the proportion of each physician's prescriptions sent electronically was calculated from the prescription records. Practice culture data were obtained from a survey of the physicians in each practice. Data were analyzed using hierarchal regression. Findings: Practice-level variables explain most of the variance in the use of e-scripts by physicians, although there are significant differences in use among specialties as well. General internists have slightly lower use rates and pediatricians have the highest rates. Larger practices and multispecialty practices have higher use rates, and five practice culture dimensions influence these rates; two have a negative influence and three (organizational trust, adaptive, and a business orientation) have a positive influence. Practice Implications: While previous studies have identified physician characteristics and product deficiencies as factors limiting the use of electronic information technologies in medical practices, our data indicate that the influence of these factors may be highly dependent on the culture of the practice. Consequently, practice administrators can improve physician acceptance and use of these technologies by making sure that there is a culture/technology fit before deciding on a product.
Clustering Functional Data using Wavelets

We present two methods for detecting patterns and clusters in high dimensional time-dependent functional data. Our methods are based on wavelet-based similarity measures, since wavelets are well suited for identifying highly discriminant local time and scale features. The multiresolution aspect of the wavelet transform provides a time-scale decomposition of the signals allowing to visualize and to cluster the functional data into homogeneous groups. For each input function, through its empirical orthogonal wavelet transform the first method uses the distribution of energy across scales generate a handy number of features that can be sufficient to still make the signals well distinguishable. Our new similarity measure combined with an efficient feature selection technique in the wavelet domain is then used within more or less classical clustering algorithms to effectively differentiate among high dimensional populations. The second method uses dissimilarity measures between the whole time-scale representations and are based on wavelet-coherence tools. The clustering is then performed using a k-centroid algorithm starting from these dissimilarities. Practical performance of these methods that jointly designs both the feature selection in the wavelet domain and the classification distance is demonstrated through simulations as well as daily profiles of the French electricity power demand.
New Learning Based Super-Resolution: Use of DWT and IGMRF Prior

In this paper, we propose a new learning-based approach for super-resolving an image captured at low spatial resolution. Given the low spatial resolution test image and a database consisting of low and high spatial resolution images, we obtain super-resolution for the test image. We first obtain an initial high-resolution (HR) estimate by learning the high-frequency details from the available database. A new discrete wavelet transform (DWT) based approach is proposed for learning that uses a set of low-resolution (LR) images and their corresponding HR versions. Since the super-resolution is an ill-posed problem, we obtain the final solution using a regularization framework. The LR image is modeled as the aliased and noisy version of the corresponding HR image, and the aliasing matrix entries are estimated using the test image and the initial HR estimate. The prior model for the super-resolved image is chosen as an Inhomogeneous Gaussian Markov random field (IGMRF) and the model parameters are estimated using the same initial HR estimate. A maximum a posteriori (MAP) estimation is used to arrive at the cost function which is minimized using a simple gradient descent approach. We demonstrate the effectiveness of the proposed approach by conducting the experiments on gray scale as well as on color images. The method is compared with the standard interpolation technique and also with existing learning-based approaches. The proposed approach can be used in applications such as wildlife sensor networks, remote surveillance where the memory, the transmission bandwidth, and the camera cost are the main constraints.
Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical–induced DNA damage

Mitochondrial protein-linked DNA repair promotes gene transcription and protects from free radical–induced DNA damage. Breakage of one strand of DNA is the most common form of DNA damage. Most damaged DNA termini require end-processing in preparation for ligation. The importance of this step is highlighted by the association of defects in the 3′-end processing enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid intermediates during chemotherapy and radiotherapy. Although much is known about the repair of PDBs in the nucleus, little is known about this process in the mitochondria. We reveal that TDP1 resolves mitochondrial PDBs (mtPDBs), thereby promoting mitochondrial gene transcription. Overexpression of a toxic form of mitochondrial topoisomerase I (TOP1mt*), which generates excessive mtPDBs, results in a TDP1-dependent compensatory up-regulation of mitochondrial gene transcription. In the absence of TDP1, the imbalance in transcription of mitochondrial- and nuclear-encoded electron transport chain (ETC) subunits results in misassembly of ETC complex III. Bioenergetics profiling further reveals that TDP1 promotes oxidative phosphorylation under both basal and high energy demands. It is known that mitochondrial dysfunction results in free radical leakage and nuclear DNA damage; however, the detection of intermediates of radical damage to DNA is yet to be shown. Consequently, we report an increased accumulation of carbon-centered radicals in cells lacking TDP1, using electron spin resonance spectroscopy. Overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) reduces carbon-centered adducts and protects TDP1-deficient cells from oxidative stress. Conversely, overexpression of the amyotrophic lateral sclerosis–associated mutant SOD1G93A leads to marked sensitivity. Whereas Tdp1 knockout mice develop normally, overexpression of SOD1G93A suggests early embryonic lethality. Together, our data show that TDP1 resolves mtPDBs, thereby regulating mitochondrial gene transcription and oxygen consumption by oxidative phosphorylation, thus conferring cellular protection against reactive oxygen species–induced damage.
Dunite distribution in the Oman Ophiolite: Implications for melt flux through porous dunite conduits

Dunites in the mantle section of the Oman ophiolite represent conduits for chemically isolated melt transport through the shallow mantle beneath oceanic spreading centers. These dunite melt conduits exhibit a scale‐invariant power law relationship between width and cumulative abundance, as measured over 4 orders of magnitude. We use this size/frequency distribution to assess several hypotheses for dunite formation and estimate the total melt flux that a dunite network can accommodate beneath an oceanic spreading center. Dunites, measured from one‐dimensional lithologic sections and digital image mosaics at a variety of length scales, range in width from ∼3 mm to ∼100 m and follow a power law with a slope of ∼1.1. Extrapolation of the power law predicts that dunites as wide as 3.5 km may exist in the melting region beneath a mid‐ocean ridge. Alternatively, perhaps the widest dunites we observe (∼100 m) represent a maximum size. Modeling of dunites as diffusive reaction zones around melt‐filled hydrofractures cannot explain the existence of dunites wider than ∼10 m in Oman. Instead, dunites may represent high porosity conduits formed by reactive porous flow. Using the observed size/frequency relationship, the assumption that dunites form a coalescing network and the requirement that flux is conserved where dunites merge, we estimate the total flux through a porous dunite network and the fraction of that flux that remains chemically isolated. Our flux model predicts that the porosity in a dunite scales with the width. For maximum porosities of ∼1–4% in the widest dunites, a network of porous dunite conduits with the abundances observed in Oman can supply a sufficient flux of melt (of which > 95% remains chemically unequilibrated with shallow residual peridotites) to satisfy the observed mid‐ocean ridge flux.
External prestressed carbon fiber-reinforced polymer straps for shear enhancement of concrete

The use of fiber-reinforced polymers (FRPs) for the strengthening and repair of existing concrete structures is a field with tremendous potential. The materials are very durable and, hence, ideally suited for use as external reinforcement. Although extensive work has been carried out investigating the use of FRPs for flexural strengthening, a fairly recent development is the use of posttensioned, nonlaminated, carbon fiber-reinforced polymer (CFRP) straps as external shear reinforcement for concrete. Experiments were carried out on an unstrengthened control beam and beams strengthened with external CFRP straps. It was found that the ultimate load capacity of the strengthened beams was significantly higher than that of the control specimen. Existing design codes and analysis methods were found to underestimate the ultimate resistance of the control specimen and the strengthened beams. Nevertheless, the modified compression field theory provided insight into possible failure mechanisms and the influence of the strap prestress level on the structural behavior. It is concluded that the use of these novel stressed elements could represent a viable and durable means of strengthening existing concrete infrastructure.
A basic introduction to the thermodynamics of the Earth system far from equilibrium and maximum entropy production

The Earth system is remarkably different from its planetary neighbours in that it shows pronounced, strong global cycling of matter. These global cycles result in the maintenance of a unique thermodynamic state of the Earth's atmosphere which is far from thermodynamic equilibrium (TE). Here, I provide a simple introduction of the thermodynamic basis to understand why Earth system processes operate so far away from TE. I use a simple toy model to illustrate the application of non-equilibrium thermodynamics and to classify applications of the proposed principle of maximum entropy production (MEP) to such processes into three different cases of contrasting flexibility in the boundary conditions. I then provide a brief overview of the different processes within the Earth system that produce entropy, review actual examples of MEP in environmental and ecological systems, and discuss the role of interactions among dissipative processes in making boundary conditions more flexible. I close with a brief summary and conclusion.
Analysis of a Stabilized Finite Element Approximation of the Transient Convection-Diffusion Equation Using an ALE Framework

In this paper we analyze a stabilized finite element method to approximate the convection-diffusion equation on moving domains using an arbitrary Lagrangian Eulerian (ALE) framework. As basic numerical strategy, we discretize the equation in time using first and second order backward differencing (BDF) schemes, whereas space is discretized using a stabilized finite element method (the orthogonal subgrid scale formulation) to deal with convection dominated flows. The semidiscrete problem (continuous in space) is first analyzed. In this situation it is easy to identify the error introduced by the ALE approach. After that, the fully discrete method is considered. We obtain optimal error estimates in both space and time in a mesh dependent norm. The analysis reveals that the ALE approach introduces an upper bound for the time step size for the results to hold. The results obtained for the fully discretized second order scheme (in time) are associated to a weaker norm than the one used for the first order method. Nevertheless, optimal convergence results have been proved. For fixed domains, we recover stability and convergence results with the strong norm for the second order scheme, stressing the aspects that make the analysis of this method much more involved.
DMPK‐associated myotonic dystrophy and CTG repeats in Alabama African Americans

Myotonic dystrophy type 1 (DM1) is a result of a CTG expansion in the 3′‐untranslated region of the DMPK gene. DM1 is rare among African blacks who have fewer large CTG repeats in the normal range than other racial/ethnic groups. Neither the prevalence of DM1 nor the relationship of CTG expansion to clinical status in African Americans (AAs) is well documented. We describe two AA brothers with DM1, each of whom had CTG repeats of 5/639; their father was reported to have DM1 and had CTG repeats of 5/60. Other family members had CTG repeats of 5–14. An unrelated AA patient from a second kinship also had DM1; an analysis revealed CTG repeats of 27/191. In 161 Alabama AA control subjects, we observed 18 CTG alleles from 5 to 28 repeats; the most common allele had five CTG repeats. The frequency of CTG repeats ≥15 were greater (p < 0.0003) in Pygmy, Amhara Ethiopian, Ashkenazi Jewish, North African Jewish, Israeli Muslim Arab, European white, and Japanese populations than in the Alabama AA population. These data suggest that the risk for DM1 in AAs is intermediate between that of African blacks and whites of European descent.
K-glypican: a novel GPI-anchored heparan sulfate proteoglycan that is highly expressed in developing brain and kidney

Glypicans are a family of glycosylphosphatidylinositol (GPI)-anchored cell surface heparan sulfate proteoglycans (HSPGs). The glypican family, which currently includes glypican, the developmentally regulated rat intestinal transcript OCI-5, and cerebroglycan, is characterized by a similar core protein size and almost complete conservation of cysteine residues. By RT-PCR using degenerate oligonucleotide primers based on the sequence homologies, we isolated mouse cDNA encoding a novel member of the glypican family as well as mouse homologues of glypican and OCI-5. The novel molecule, named K- glypican, has a predicted molecular mass of 57.5 kD and potential attachment sites for heparan sulfate chains and a GPI anchor in its COOH-terminal region, like other members of the glypican family. Transfection of an epitope-tagged full-length K-glypican cDNA into MDCK cells demonstrated that K-glypican is indeed expressed as a GPI- anchored HSPG. Northern blot analyses with K-glypican, glypican, and OCI-5 probes demonstrated that kidney and developing brain, and that these three molecules show remarkable patterns of cell type- and developmental stage-specific expression. In situ hybridization revealed that the major sites of K-glypican expression in developing embryo are tubular epithelial cells in the kidney and proliferating neuroepithelial cells in the brain. These results indicate that K- glypican is a novel GPI-anchored HSPG involved in embryonic development.