Miracle-dz/UniFAR-FTUs huggingface dataset:
Value of improved lipid control in patients at high risk for adverse cardiac events.

OBJECTIVES Lipid-lowering therapy (LLT) is suboptimally used in patients with hyperlipidemia in the 2 highest statin benefit groups (SBGs), as categorized by the American College of Cardiology and the American Heart Association. This study estimated the social value of reducing low-density lipoprotein cholesterol (LDL-C) levels by 50% for patients in SBGs 1 and 2 who have been treated with standard LLT but have not reached LDL-C goal, as well as the potential value of PCSK9 inhibitors for patients in these groups. STUDY DESIGN Simulation model. METHODS We used National Health and Nutrition Examination Surveys (NHANES) and US Census data to project the population of SBGs 1 and 2 in the time period 2015 to 2035. We used insurance claims data to estimate incidence rates of major adverse cardiac events (MACEs), and NHANES with National Vital Statistics data to estimate cardiovascular disease mortality rates. Using established associations between LDL-C and MACE risk, we estimated the value of reducing LDL-C levels by 50%. We incorporated results from a meta-analysis to estimate the value of PSCK9 inhibitors. RESULTS Among those treated with LLT with LDL-C > 70 mg/dL in SBGs 1 and 2, the cumulative value of reducing LDL-C levels by 50% would be $2.9 trillion from 2015 to 2035, resulting primarily from 1.6 million deaths averted. The cumulative value of PCSK9 inhibitors would range from $3.4 trillion to $5.1 trillion (1.9-2.8 million deaths averted), or $12,000 to $17,000 per patient-year of treatment. CONCLUSIONS Lowering LDL-C in high-risk patients with hyperlipidemia has enormous potential social value. For patients in these high-risk groups, PCSK9 inhibitors may have considerable net value depending on the final prices payers ultimately select.
Racial/ethnic differences in hypertension prevalence, treatment, and control for outpatients in northern California 2010-2012.

BACKGROUND Hypertension (HTN) is a known major cardiovascular disease risk factor, but prevalence, treatment, and control of HTN among rapidly growing minority groups such as Asian Americans and Hispanics are unknown largely due to either underrepresentation in epidemiologic studies or aggregation of Asian American subgroups. METHODS A three-year cross-section (2010-2012) of patients from a large ambulatory care setting in northern California was examined in the following subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Mexicans, non-Hispanic Blacks (NHBs), and non-Hispanic Whites (NHWs). We defined HTN as two separate nonemergent office visit blood pressure measurements ≥140/90 mm Hg, physician diagnosis of HTN, or use of antihypertensive medications. RESULTS A total of 208,985 patients were included in the study. Age-adjusted HTN prevalence ranged from 30.0% in Chinese women to 59.9% in Filipino men. Most minority subgroups had lower or similar odds of having HTN compared with NHWs, except for Filipinos and NHBs whose odds were significantly higher after adjusting for patient demographic and clinical characteristics. Asian Americans and NHBs were more likely to be treated for HTN compared with NHWs. Achievement of blood pressure control was lower among Filipino women (odds ratio = 0.82, 99% confidence interval 0.70-0.96) and NHB men (odds ratio = 0.73, 99% confidence interval 0.58-0.91), compared with NHW women and men. CONCLUSIONS Substantial racial/ethnic variation in HTN prevalence, treatment, and control was found in our study population. Filipino and NHB women and men are at especially high risk for HTN and may have more difficulty in achieving adequate blood pressure control.
Correlation of ESAT-6-Specific Gamma Interferon Production with Pathology in Cattle following Mycobacterium bovis BCG Vaccination against Experimental Bovine Tuberculosis

ABSTRACT Vaccine development and the understanding of the pathology of bovine tuberculosis in cattle would be greatly facilitated by the definition of immunological correlates of protection and/or pathology. To address these questions, cattle were vaccinated with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and were then challenged with virulent M. bovis. Applying a semiquantitative pathology-scoring system, we were able to demonstrate that BCG vaccination imparted significant protection by reducing the disease severity on average by 75%. Analysis of cellular immune responses following M. bovis challenge demonstrated that proliferative T-cell and gamma interferon (IFN-γ) responses towards the M. bovis-specific antigen ESAT-6, whose gene is absent from BCG, were generally low in vaccinated animals but were high in all nonvaccinated calves. Importantly, the amount of ESAT-6-specific IFN-γ measured by enzyme-linked immunosorbent assay after M. bovis challenge, but not the frequency of responding cells, correlated positively with the degree of pathology found 18 weeks after infection. Diagnostic reagents based on antigens not present in BCG, like ESAT-6 and CFP-10, were still able to distinguish BCG-vaccinated, diseased animals from BCG-vaccinated animals without signs of disease. In summary, our results suggest that the determination of ESAT-6-specific IFN-γ, while not a direct correlate of protection, constitutes nevertheless a useful prognostic immunological marker predicting both vaccine efficacy and disease severity.
Likelihood‐based inferences about the mean area under a longitudinal curve in the presence of observations subject to limits of detection

Comparison of groups in longitudinal studies is often conducted using the area under the outcome versus time curve. However, outcomes may be subject to censoring due to a limit of detection and specific methods that take informative missingness into account need to be applied. In this article, we present a unified model‐based method that accounts for both the within‐subject variability in the estimation of the area under the curve as well as the missingness mechanism in the event of censoring. Simulation results demonstrate that our proposed method has a significant advantage over traditionally implemented methods with regards to its inferential properties. A working example from an AIDS study is presented to demonstrate the applicability of our approach. Copyright © 2015 John Wiley & Sons, Ltd.
MiR423-5p As a Circulating Biomarker for Heart Failure

Rationale: Aberrant expression profiles of circulating microRNAs (miRNAs) have been described in various diseases and provide high sensitivity and specificity. We explored circulating miRNAs as potential biomarkers in patients with heart failure (HF). Objective: The goal of this study was to determine whether miRNAs allow to distinguish clinical HF not only from healthy controls but also from non-HF forms of dyspnea. Methods and Results: A miRNA array was performed on plasma of 12 healthy controls and 12 HF patients. From this array, we selected 16 miRNAs for a second clinical study in 39 healthy controls and in 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF and 20 were diagnosed with dyspnea attributable to non–HF-related causes. This revealed that miR423-5p was specifically enriched in blood of HF cases and receiver-operator-characteristics (ROC) curve analysis showed miR423-5p to be a diagnostic predictor of HF, with an area under the curve of 0.91 (P<0.001). Five other miRNAs were elevated in HF cases but also slightly increased in non-HF dyspnea cases. Conclusion: We identify 6 miRNAs that are elevated in patients with HF, among which miR423-5p is most strongly related to the clinical diagnosis of HF. These 6 circulating miRNAs provide attractive candidates as putative biomarkers for HF.
The Development of Eating Disorders After Bariatric Surgery

Surgical treatment for morbid obesity can be very effective in terms of weight loss and reduction of psychopathology. But the (re)emergence of eating problems after surgery is still poorly understood and may be underreported. We describe three cases in which eating disorder symptoms developed after bariatric surgery. The accelerated weight loss and heightened dieting restraint, as well as the systematic reminders to control the amount of food eaten which are crucial for treatment success, might trigger the development of eating disorders after surgery. Implications for pre-surgery assessment and preparation are discussed.
Analytical Design of PI Controllers for Third Order Plus Time Delay Systems

This study proposes an analytical design method of a Proportional Integral controller for the stability and performance of first order plus time delay systems. The method proposed in the study achieves general computation equations for such systems. Inspired from Bode’s ideal loop, gain crossover frequency and phase margin specifications are considered for the system. Then, these specifications are used to obtain the parameters of the proportional integral controller. Analytically derived formulas by the proposed method are tested with existing plants in the literature and the results are illustrated graphically. It is shown that the tuning method satisfies desired gain crossover frequency and phase margin specifications.
Treatment of Dialysis Patients with Chronic Hepatitis C Using Pegylated Interferon and Low-Dose Ribavirin

Background No safe and effective therapy exists for chronic hepatitis C in dialysis patients. Available data on the antiviral treatment of hepatitis C in dialysis population is mostly based on standard interferon monotherapy. Objectives We conducted a prospective, cohort trial with combined therapy (pegylated-interferon-alpha-2a (135 mcg/week) plus low dose ribavirin (200 mg/day)) for chronic hepatitis C in 15 patients undergoing long-term dialysis. Twelve patients had HCV genotype 1a/1b, three were co-infected with human immunodeficiency virus (HIV), and two had compensated cirrhosis. End-points were sustained viral response and adverse effects. Results Sustained virological response was obtained in four patients (including two with HCV genotype 1); the SVR rate was 28.6% (4/14), on an intention-to-treat analysis. One subject with SVR had compensated cirrhosis. All HIV co-infected patients had well controlled HIV and one of them (33%) reached SVR. Seven (50%) of the 14 patients were non-responders, two of which relapsed after discontinuation of therapy. Drop-out rate was 71.4% (10/14). The most frequent side-effect was anemia, which required ribavirin discontinuation in three patients; seven (47%) patients received blood transfusions. Two patients died (week 4 and 14) of causes related to cardiovascular disease, which was frequent in our cohort. Two subjects were hospitalized and discontinued therapy (week 1, and 27). Conclusions Results from this study showed that about one-third of HD patients achieved sustained virological response with pegylated-interferon-alpha-2a plus low-dose ribavirin; however, tolerance to antiviral treatment was unsatisfactory. Well-controlled HIV infection should not be a contraindication to HCV therapy in dialysis patients. Prospective, controlled clinical trials of combined antiviral therapy targeted at HCV in chronic kidney disease population are indicated.
Potential for biogeochemical cycling of sulfur, iron and carbon within massive sulfide deposits below the seafloor.

Seafloor massive sulfides are a potential energy source for the support of chemosynthetic ecosystems in dark, deep-sea environments; however, little is known about microbial communities in these ecosystems, especially below the seafloor. In the present study, we performed culture-independent molecular analyses of sub-seafloor sulfide samples collected in the Southern Mariana Trough by drilling. The depth for the samples ranged from 0.52 m to 2.67 m below the seafloor. A combination of 16S rRNA and functional gene analyses suggested the presence of chemoautotrophs, sulfur-oxidizers, sulfate-reducers, iron-oxidizers and iron-reducers. In addition, mineralogical and thermodynamic analyses are consistent with chemosynthetic microbial communities sustained by sulfide minerals below the seafloor. Although distinct bacterial community compositions were found among the sub-seafloor sulfide samples and hydrothermally inactive sulfide chimneys on the seafloor collected from various areas, we also found common bacterial members at species level including the sulfur-oxidizers and sulfate-reducers, suggesting that the common members are widely distributed within massive sulfide deposits on and below the seafloor and play a key role in the ecosystem function.
Interactions of the N-terminal Domain of Ribosomal Protein L11 with Thiostrepton and rRNA*

Ribosomal protein L11 has two domains: the C-terminal domain (L11-C76) binds rRNA, whereas the N-terminal domain (L11-NTD) may variously interact with elongation factor G, the antibiotic thiostrepton, and rRNA. To begin to quantitate these interactions, L11 from Bacillus stearothermophilus has been overexpressed and its properties compared with those of L11-C76 alone in a fluorescence assay for protein-rRNA binding. The assay relies on 2′-amino-butyryl-pyrene-uridine incorporated in a 58-nucleotide rRNA fragment, which gives ∼15-fold enhancement when L11 or L11-C76 is bound. Although the pyrene tag weakens protein binding, unbiased protein-RNA association constants were obtained in competition experiments with untagged RNA. It was found that (i) intact B. stearothermophilus L11 binds rRNA with K ≈ 1.2 × 109 m-1 in buffers with 0.2 m KCl, about 100-fold tighter than Escherichia coli L11; (ii) the N-terminal domain makes a small, salt-dependent contribution to the overall L11-RNA binding affinity (∼8-fold enhancement at 0.2 m KCl), (iii) L11 stimulates thiostrepton binding by 2.3 ± 0.6 × 103-fold, predicting an overall thiostrepton affinity for the ribosome of ∼109 m-1, and (iv) the yeast homolog of L11 shows no stimulation of thiostrepton binding. The latter observation resolves the question of why eukaryotes are insensitive to the antibiotic. These measurements also show that it is plausible for thiostrepton to compete directly with EF-G·GDP for binding to the L11-RNA complex, and provide a quantitative basis for further studies of L11 function and thiostrepton mechanism.
An Ultra-Compact, Low-Power Reference Circuit/Dosimeter for Space Environments

This paper presents a compact 4-transistor reference circuit, which has been designed in a regular commercially available CMOS process, that responds linearly to radiation exposure and is suitable for compensating radiation-induced deterioration/drift of analog circuits operated in space environments. The paper includes background theory, analysis and measured results obtained from the circuit.
Oxygen transfer enhancement in aqueous/perfluorocarbon fermentation systems: I. experimental observations

A new fiber‐optic dissolved oxygen sensing technique was applied to the study of two‐phase aqueous/perfluorocarbon (pfc) dispersions. These dispersions were examined for their oxygen transfer enhancement capability in the absence and presence of an oxygen‐consuming reaction. For the pfc‐in‐water dispersions, oxygen uptake rate (OUR) enhancements were equal both with and without oxygen‐consuming cells present in the aqueous phase. In contrast, for water‐in‐pfc dispersions, OUR enhancements inthe presence of reaction were limited by oxygen diffusion across the aqueous phase droplets. Nevertheless, enhancement factors of 5–10 on an aqueous phase volume basis were obtained in a 75% pfc dispersion.These oxygen transfer enhancements were directly translatable into enhancements in overall fermenter productivity for actual microbial cultivation systems.
The Role Of Negative Numbers In The Development Of Double Entry Bookkeeping - A Comment

Peters and Emery [1978] drew on the work of Boyer [1968], Cajori [1919], and Kline [1972] for evidence of the acceptance and use of negative numbers prior to the publication of Pacioli's Summa in 1494. Their space-time continuum started at the first century in China, then moved to a seventh-century Sanskrit manuscript attributed to the Hindu mathematician Brahmagupta, followed by "the Arabs," in particular Omar Khayyam, and concluded with Pacioli. The purpose of their spacetime continuum was to build a case and prove that negative numbers were not accepted in Europe at the time double entry was developed and publicized and to conclude that as a consequence the method treated all account balances as positive. In contrast, I draw on the primary source Pacioli [1494] and refer to the work of Leonardo of Pisa (b. ca. 1170) to demonstrate that the rules of computation for both positive and negative numbers were known in Europe before the publication of the Summa. Peters and Emery [1978] presented evidence that negative numbers were accepted and used in the Orient in the first millennium and sought to show that their acceptance and use in India died out due to the influence of Omar Khayyam (ca. 1048-ca. 1131). They implied that the rules of computation defined by Brahmagupta (b. 598) and restated by Bhdskara II (b. 1115) were not transferred to the Occident by the Arabs when they revealed the mathematical knowledge of the classical Greeks and the East to medieval European scholars and traders. They supported this implication by stating that Pacioli's work on arithmetic which described "the then-current state of mathematical technology . did not recognize negative numbers" [1978, p. 425].
Analysis of Factors Associated with Subjective Fatigue Among Motorcycle Drivers in Online Ojek

Background: The number of deaths from traffic accidents is fifth level in Indonesia. 72% traffic accidents in Indonesia involving motorcycles according data in 2011. Fatigue is one of the causes of motorcycle accidents. The development of online ojek is quite rapid and is dominated by motorbikes as a means of transportation so that this development requires attention especially concerning the safety of passengers and their own drivers. The purpose of this study aims to analyze several factors related to subjective fatigue among motorcycle drivers on online ojek. Methods: The study was conducted in Bekasi in 2017 using quantitative methods and cross-sectional research designs. The populations in this study were all motorcycle drivers on online ojek with a sample of 106 respondents taken by accidental sampling technique. Subjective fatigue is measured by the Industrial Fatigue Research Committee (IFRC). The analysis was carried out by univariate and bivariate using Chi-Square Test (X²) Results: The level of subjective fatigue is at low level (50.9%), moderate (42.5%), and only 6.6% at high levels. Respondents were more than 35 years of age, worked less than 10 hours, slept less than 8 hours, had no disease history, and made online ojek as their main job. The results of the bivariate analysis found of disease history that was significantly associated with subjective fatigue (p = 0.011, OR = 0.3; CI 95% = 0.1-0.7), while the other variables were not related even though the analysis of cross tables there is a tendency to relate. Conclusions and Suggestions: Disease history is a protective factor for the occurrence of subjective fatigue among motorbike drivers on online ojek, so increased awareness of prevention efforts must continue to be encouraged because the results of this study indicate that the community has just behaved healthily after they are sick. Keywords: subjective fatique, motorcycle driver, online ojek, traffic accident
Suggested modifications for disk diffusion susceptibility testing criteria for levofloxacin and sparfloxacin following tests with a predictor panel of ciprofloxacin-resistant clinical isolates

A predictor panel of 300 clinical bacterial isolates (200 resistant to ciprofloxacin) was used to compare 5-micrograms disk diffusion test results with the MICs of ofloxacin (control), levofloxacin, and sparfloxacin. Regression analysis demonstrated high correlations between the methods for all three fluoroquinolones (r > or = 0.95). In order to minimize disk diffusion testing errors among the fluoroquinolone-resistant strains, the following modifications to previously proposed or published interpretive criteria were suggested: for levofloxacin, susceptible at > or = 17 mm (< or = 2 micrograms/ml) and resistant at < or = 13 mm (> or = 8 micrograms/ml); for sparfloxacin, susceptible at > or = 20 mm (< or = 1 microgram/ml) and resistant at < or = 16 mm (> or = 4 micrograms/ml). The study control drug, ofloxacin, did not appear to possess a significant error rate (5% minor error) when fluoroquinolone-resistant strains were tested, and no modifications were proposed. Under these proposed interpretive criteria, the absolute categorical agreements between standardized susceptibility testing methods for levofloxacin and sparfloxacin results were 91.3 and 94.0%, respectively (< or = 0.3% major errors and nil very major errors).
Telomeres: The silence is broken

The ends of linear eukaryotic chromosomes, telomeres, distinguish natural chromosome ends from DNA double stranded breaks and thus promote genome stability. Telomeres comprise a repetitive DNA skeleton, which is wrapped in specific protein complexes. Recent data indicate that an additional building block of telomeres is RNA and that the longstanding idea that telomeres are silent genomic regions needs to be overturned. Mammalian telomeres are indeed transcribed into RNA molecules, which remain associated with telomeric chromatin, suggesting RNA-mediated mechanisms in organizing telomere architecture.
Parent-progeny imputation from pooled samples for cost-efficient genotyping in plant breeding

The increased usage of whole-genome selection (WGS) and other molecular evaluation methods in plant breeding relies on the ability to genotype a very large number of untested individuals in each breeding cycle. Many plant breeding programs evaluate large biparental populations of homozygous individuals derived from homozygous parent inbred lines. This structure lends itself to parent-progeny imputation, which transfers the genotype scores of the parents to progeny individuals that are genotyped for a much smaller number of loci. Here we introduce a parent-progeny imputation method that infers individual genotypes from index-free pooled samples of DNA of multiple individuals using a Hidden Markov Model (HMM). We demonstrated the method for pools of simulated maize double haploids (DH) from biparental populations, genotyped using a genotyping by sequencing (GBS) approach for 3,000 loci at 0.125x to 4x coverage. We observed high concordance between true and imputed marker scores and the HMM produced well-calibrated genotype probabilities that correctly reflected the uncertainty of the imputed scores. Genomic estimated breeding values (GEBV) calculated from the imputed scores closely matched GEBV calculated from the true marker scores. The within-population correlation between these sets of GEBV approached 0.95 at 1x and 4x coverage when pooling two or four individuals, respectively. Our approach can reduce the genotyping cost per individual by a factor up to the number of pooled individuals in GBS applications without the need for extra sequencing coverage, thereby enabling cost-effective large scale genotyping for applications such as WGS in plant breeding.