Miracle-dz/UniFAR-FTUs huggingface dataset:
Racial/Ethnic Disparity in NICU Quality of Care Delivery

By using the Baby-MONITOR, a composite indicator of NICU quality, the authors of this study examined racial and/or ethnic disparities. BACKGROUND: Differences in NICU quality of care provided to very low birth weight (<1500 g) infants may contribute to the persistence of racial and/or ethnic disparity. An examination of such disparities in a population-based sample across multiple dimensions of care and outcomes is lacking. METHODS: Prospective observational analysis of 18 616 very low birth weight infants in 134 California NICUs between January 1, 2010, and December 31, 2014. We assessed quality of care via the Baby-MONITOR, a composite indicator consisting of 9 process and outcome measures of quality. For each NICU, we calculated a risk-adjusted composite and individual component quality score for each race and/or ethnicity. We standardized each score to the overall population to compare quality of care between and within NICUs. RESULTS: We found clinically and statistically significant racial and/or ethnic variation in quality of care between NICUs as well as within NICUs. Composite quality scores ranged by 5.26 standard units (range: −2.30 to 2.96). Adjustment of Baby-MONITOR scores by race and/or ethnicity had only minimal effect on comparative assessments of NICU performance. Among subcomponents of the Baby-MONITOR, non-Hispanic white infants scored higher on measures of process compared with African Americans and Hispanics. Compared with whites, African Americans scored higher on measures of outcome; Hispanics scored lower on 7 of the 9 Baby-MONITOR subcomponents. CONCLUSIONS: Significant racial and/or ethnic variation in quality of care exists between and within NICUs. Providing feedback of disparity scores to NICUs could serve as an important starting point for promoting improvement and reducing disparities.
Design considerations and rationale of a multi-center trial to sustain weight loss: the weight loss maintenance trial

Background The Weight Loss Maintenance Trial (WLM) is a multi-center, randomized, controlled trial that compares the effects of two 30-month maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology (IT) to a self-directed usual care control group (SD), in overweight or obese individuals who are at high risk for cardiovascular disease. Purpose This paper provides an overview of the design and methods, and design considerations and lessons learned from this trial. Methods All participants received a 6-month behavioral weight loss program consisting of weekly group sessions. Participants who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC condition provided monthly contacts with an interventionist primarily via telephone and quarterly face-to-face visits. The IT condition provided frequent, individualized contact through a tailored, website system. Both the PC and IT maintenance programs encouraged the DASH dietary pattern and employed theory-based behavioral techniques to promote maintenance. Results Design considerations included choice of study population, frequency and type of intervention visits, and choice of primary outcome. Overweight or obese persons with CVD risk factors were studied. The pros and cons of studying this population while excluding others are presented. We studied intervention contact strategies that made fewer demands on participant time and travel, while providing frequent opportunities for interaction. The primary outcome variable for the trial was change in weight from randomization to end of follow-up (30 months). Limitations Limits to generalizability are discussed. Individuals in need of weight loss strategies may have been excluded due to barriers associated with internet use. Other participants may have been excluded secondary to a comorbid condition. Conclusions This paper highlights the design and methods of WLM and informs readers of discussions of critical issues and lessons learned from the trial. Clinical Trials 2008; 5: 546—556. http://ctj.sagepub. com
Soluble CD14 levels, interleukin 6, and mortality among prevalent hemodialysis patients.

BACKGROUND CD14 is a pattern-recognition receptor that has a central immunomodulatory role in proinflammatory signaling in response to a variety of ligands, including endotoxin. CD14 protein is present in 2 forms: soluble (sCD14) and membrane bound. Here, we studied the implications of increased sCD14 levels in hemodialysis patients. We hypothesized that sCD14 level increase may link to cytokine activation and protein-energy wasting, predisposing to increased mortality risk. STUDY DESIGN Prospective observational study of prevalent hemodialysis patients. SETTING & PARTICIPANTS 211 prevalent hemodialysis patients, median age of 65 years, with 29 months of vintage dialysis time followed up for mortality for a median of 31 months. PREDICTORS Tertiles of baseline circulating sCD14 levels corresponding to less than 2.84, 2.85 to 3.62, and greater than 3.63 microg/mL. OUTCOME The major outcome of interest was all-cause mortality. MEASUREMENTS sCD14 and endotoxin, together with other markers of inflammation and protein-energy wasting. RESULTS Median sCD14 level was 3.2 microg/mL (25th to 75th percentile, 2.7 to 3.9). sCD14 level correlated positively with C-reactive protein, interleukin 6, endotoxin, and pentraxin 3 levels and negatively with serum albumin level, muscle mass, and handgrip strength. Patients with increased sCD14 levels had lower body mass index and increased prevalence of muscle atrophy. Patients within the highest sCD14 tertile had a crude morality hazard ratio of 1.94 (95% confidence interval, 1.13 to 3.32) that persisted after adjustment for multiple confounders (hazard ratio, 3.11; 95% confidence interval, 1.49 to 6.46). In patients with persistent inflammation, the presence of a concurrent sCD14 level increase gradually increased mortality risk, but this effect was less than multiplicative and failed to show a statistical interaction. LIMITATIONS Those inherent to an observational study. CONCLUSIONS sCD14 level is associated with inflammation and protein-energy wasting in hemodialysis patients. It is a strong and independent predictor of mortality that warrants further assessment in the clinical setting regarding its usefulness as a complementary prognosticator to other general inflammatory markers.
Transmission of Hepatitis C Virus Among HIV-Positive Homosexual Men and Response to a 24-Week Course of Pegylated Interferon and Ribavirin

Objective:To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. Design:Open-label, prospective study conducted in London, January 1997-December 2003. Methods:Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon α-2b 1.5 μg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. Results:Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4+ count (P = 0.029), CD4+ count >500 cells/mm3 (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). Conclusions:Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.
Semiquinone and Cluster N6 Signals in His-tagged Proton-translocating NADH:Ubiquinone Oxidoreductase (Complex I) from Escherichia coli*

Background: Complex I is the largest proton pump in mitochondria, yet its mechanism is unknown. Results: For the first time, inhibitor-sensitive semiquinone and cluster N6 signals were detected in affinity-purified E. coli complex I. Conclusion: The semiquinone species is involved in the redox-driven proton-pumping mechanism. Significance: Our highly pure complex I will help advance the mechanistic study of the protein. NADH:ubiquinone oxidoreductase (complex I) pumps protons across the membrane using downhill redox energy. The Escherichia coli complex I consists of 13 different subunits named NuoA-N coded by the nuo operon. Due to the low abundance of the protein and some difficulty with the genetic manipulation of its large ∼15-kb operon, purification of E. coli complex I has been technically challenging. Here, we generated a new strain in which a polyhistidine sequence was inserted upstream of nuoE in the operon. This allowed us to prepare large amounts of highly pure and active complex I by efficient affinity purification. The purified complex I contained 0.94 ± 0.1 mol of FMN, 29.0 ± 0.37 mol of iron, and 1.99 ± 0.07 mol of ubiquinone/1 mol of complex I. The extinction coefficient of isolated complex I was 495 mm−1 cm−1 at 274 nm and 50.3 mm−1 cm−1 at 410 nm. NADH:ferricyanide activity was 219 ± 9.7 μmol/min/mg by using HEPES-Bis-Tris propane, pH 7.5. Detailed EPR analyses revealed two additional iron-sulfur cluster signals, N6a and N6b, in addition to previously assigned signals. Furthermore, we found small but significant semiquinone signal(s), which have been reported only for bovine complex I. The line width was ∼12 G, indicating its neutral semiquinone form. More than 90% of the semiquinone signal originated from the single entity with P½ (half-saturation power level) = 1.85 milliwatts. The semiquinone signal(s) decreased by 60% when with asimicin, a potent complex I inhibitor. The functional role of semiquinone and the EPR assignment of clusters N6a/N6b are discussed.
Antioxidant and neuroprotector effect of Lepidium meyenii (maca) methanol leaf extract against 6-hydroxy dopamine (6-OHDA)-induced toxicity in PC12 cells

Abstract Reactive oxygen species (ROS) are normally produced during cell metabolism, there is strong evidence to suggest that ROS produced in excess impair the cell and may be etiologically related to various neurodegenerative diseases. This study was undertaken to examine the effects of Lepidium meyenii (MACA) methanol leaf extract on neurotoxicity in PC12 cell exposed to 6-hydroxydopamine (6-OHDA). Fresh samples of “maca” leaves were processed in order to obtain foliar extracts and to evaluate the neurobiological activity on PC12 cells, subjected to the cytotoxic effect of 6-OHDA through the determination of the capacity antioxidant, cell viability and cytotoxicity assays on PC12 cells. The results of the tests of antioxidant activity, showed maximum values of 2262.37 and 1305.36 expressed in Trolox equivalents (TEAC), for the methanolic and aqueous fractions respectively. Cell viability assays at a dose of 10 μg extract showed an increase of 31% and 60% at 6 and 12 h of pretreatment, respectively. Cytotoxicity assays at the same dose and exposure time showed a 31.4% and 47.8% reduction in lactate dehydrogenase (LDH) activity and an increase in superoxide dismutase (SOD) activity. The results allow us to affirm that the methanolic foliar extract of “maca” presents in vitro neurobiological activity of antioxidant protection, increase in cell viability and reduction of cytotoxicity against oxidative stress generated by 6-OHDA. In conclusion, the present study shows a protective role for Lepidium meyenii leaf extract on 6-OHDA-induced toxicity by an antioxidant effect.
Fixed Capital as a Joint Product

Since the Reswitching Debate the point has become familiar that the means of production in a capitalist society represent different ‘quantities of capital’ depending on the prevailing rate of profit. But because these discussions were about a critique of the neoclassical theory of value and distribution and not about a new comprehensive theory of capital, they have been conducted either in terms of circulating capital without machines or in terms of production by means of one machine at different ages (cf. Hicks, 1970, Nuti, 1970). Although von Neumann and Sraffa revived the ‘old classical idea’ (Sraffa) of treating what is left at the end of the year’s process of production as an economically different good from the one which entered the process, very few1 have tried to construct models with several fixed capital goods which are explicitly distinguished from other kinds of joint products.
The role of the placenta in thyroid hormone delivery to the fetus

The transplacental passage of thyroid hormones from the maternal circulation to the fetal circulation within the human hemochorial placenta is important for normal fetal development, particularly the development of the central nervous system. The role of maternal thyroid hormones is particularly important in the first half of pregnancy, before the onset of endogenous thyroid hormone production in the fetus. The human placenta regulates the quantity and composition of different forms of transported thyroid hormones to ensure that the requisite levels are present in the fetus for each stage of development. Transplacental thyroid hormone supply to the fetus is modulated by several factors, including the following proteins: plasma membrane transporters, which regulate the passage of thyroid hormones in and out of cells; iodothyronine deiodinases, which metabolize thyroid hormones; and proteins within trophoblast cells, which bind thyroid hormones. In pathological situations of either maternal or fetal thyroid hormone deficiency during pregnancy, the placenta seems to lack the full compensatory mechanisms necessary to optimize maternal–fetal transfer of thyroid hormones. Inadequate passage of thyroid hormones can lead to suboptimal fetal thyroid hormone levels, which might contribute to the neurodevelopmental delay associated with such conditions. Thus, maintaining normal maternal thyroid hormone status is likely to be the primary factor in ensuring adequate transplacental thyroid hormone passage and appropriate iodide supply to the fetus.
Clinical pharmacology of tocilizumab for the treatment of patients with rheumatoid arthritis

Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody for the treatment of rheumatoid arthritis (RA). A dose of 8 mg/kg produces adequate blockade of IL-6 receptors throughout a dosing interval, as confirmed by sustained high levels of tocilizumab-bound soluble IL6-R complex and normalization of C-reactive protein levels. Studies have confirmed 8 mg/kg every 4 weeks as the optimal dose and 4 mg/kg as the starting dose for the treatment of RA, with favorable efficacy and acceptable safety profiles. After 8 mg/kg, steady-state peak and trough concentrations were 183 ± 86 and 9.7 ± 11 µg/ml, respectively. Tocilizumab serum exposures increased more than proportionally to the dose increase from 2–10 mg/kg. Total clearance is concentration dependent, with non-linear receptor-mediated clearance dominant at low concentrations (<25 µg/ml). Tocilizumab exposures are not affected by common concomitant medications in RA patients, but decreased IL-6 activity resulted in increased CYP3A4 activity and hence decreased exposures of CYP3A4 substrates.
Rates and Mechanisms of Resistance Development in Mycobacterium tuberculosis to a Novel Diarylquinoline ATP Synthase Inhibitor

ABSTRACT R207910 (also known as TMC207) is an investigational drug currently in clinical studies for the treatment of multidrug-resistant (MDR) tuberculosis. It has a high degree of antimycobacterial activity and is equally effective against drug-susceptible and MDR Mycobacterium tuberculosis isolates. In the present study, we characterized the development of resistance to R207910 in vitro. Ninety-seven independent R207910-resistant mutants were selected from seven different clinical isolates of M. tuberculosis (three drug-susceptible and four MDR isolates) at 10×, 30×, and 100× the MIC. At a concentration of 0.3 mg/liter (10× the MIC), the mutation rates ranged from 4.7 × 10−7 to 8.9 × 10−9 mutations per cell per division, and at 1.0 mg/liter (30× the MIC) the mutation rate ranged from 3.9 × 10−8 to 2.4 × 10−9. No resistant mutants were obtained at 3 mg/liter (100× the MIC). The level of resistance ranged from 0.12 to 3.84 mg/liter for the mutants identified; these concentrations represent 4- to 128-fold increases in the MICs. For 53 of the resistant mutants, the atpE gene, which encodes a transmembrane and oligomeric C subunit of the ATP synthase and which was previously shown to be involved in resistance, was sequenced. For 15/53 mutants, five different point mutations resulting in five different amino acid substitutions were identified in the atpE gene. For 38/53 mutants, no atpE mutations were found and sequencing of the complete F0 ATP synthase operon (atpB, atpE, and atpF genes) and the F1 ATP synthase operon (atpH, atpA, atpG, atpD, and atpC genes) from three mutants revealed no mutations, indicating other, alternative resistance mechanisms. Competition assays showed no measurable reduction in the fitness of the mutants compared to that of the isogenic wild types.
Systematic Review and Meta‐Analysis of the Impact of Computed Tomography–Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation

Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)‐assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta‐analysis on the impact of CT‐assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11–3.05, p = 0.02) and 1.72 (95% confidence interval 0.99–3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End‐stage Liver Disease score. Less‐consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment.
Try to Look on the Bright Side: Children and Adults Can (Sometimes) Override Their Tendency to Prioritize Negative Faces

We used eye tracking to examine 4- to 10-year-olds’ and adults’ (N = 173) visual attention to negative (anger, fear, sadness, disgust) and neutral faces when paired with happy faces in 2 experimental conditions: free-viewing (“look at the faces”) and directed (“look only at the happy faces”). Regardless of instruction, all age groups more often looked first to negative versus positive faces (no age differences), suggesting that initial orienting is driven by bottom-up processes. In contrast, biases in more sustained attention—last looks and looking duration—varied by age and could be modified by top-down instruction. On the free-viewing task, all age groups exhibited a negativity bias which attenuated with age and remained stable across trials. When told to look only at happy faces (directed task), all age groups shifted to a positivity bias, with linear age-related improvements. This ability to implement the “look only at the happy faces” instruction, however, fatigued over time, with the decrement stronger for children. Controlling for age, individual differences in executive function (working memory and inhibitory control) had no relation to the free-viewing task; however, these variables explained substantial variance on the directed task, with children and adults higher in executive function showing better skill at looking last and looking longer at happy faces. Greater anxiety predicted more first looks to angry faces on the directed task. These findings advance theory and research on normative development and individual differences in the bias to prioritize negative information, including contributions of bottom-up salience and top-down control.
Colonisation of the developing human brain and spinal cord by microglia: a review

Microglia are the immune effector cells of the nervous system. The prevailing view is that microglia are derived from circulating precursors in the blood, which originate from the bone‐marrow. Colonisation of the central nervous system (CNS) by microglia is an orchestrated response during human fetal development related to the maturation of the nervous system. It coincides with vascularisation, formation of radial glia, neuronal migration and myelination primarily in the 4th–5th months and beyond. Microglial influx generally conforms to a route following white matter tracts to gray areas. We have observed that colonisation of the spinal cord begins around 9 weeks, with the major influx and distribution of microglia commencing around 16 weeks. In the cerebrum, colonisation is in progress during the second trimester, and ramified microglial forms are widely distributed within the intermediate zone by the first half of intra‐uterine life (20–22 weeks). A distinct pattern of migration occurs along radial glia, white matter tracts and vasculature. The distribution of these cells is likely to be co‐ordinated by spatially and temporally regulated, anatomical expression of chemokines including RANTES and MCP‐1 in the cortex; by ICAM‐2 and PECAM on radiating cerebral vessels and on capillaries within the germinal layer, and apoptotic cell death overlying this region. The phenotype and functional characteristics of fetal microglia are also outlined in this review. The need for specific cellular interactions and targeting is greater within the central nervous system than in other tissues. In this respect, microglia may additionally contribute towards CNS histogenesis. Microsc. Res. Tech. 45:359–382, 1999. © 1999 Wiley‐Liss, Inc.
A Note on Learning Algorithms for Quadratic Assignment with Graph Neural Networks

Inverse problems correspond to a certain type of optimization problems formulated over appropriate input distributions. Recently, there has been a growing interest in understanding the computational hardness of these optimization problems, not only in the worst case, but in an average-complexity sense under this same input distribution. In this revised note, we are interested in studying another aspect of hardness, related to the ability to learn how to solve a problem by simply observing a collection of previously solved instances. These 'planted solutions' are used to supervise the training of an appropriate predictive model that parametrizes a broad class of algorithms, with the hope that the resulting model will provide good accuracy-complexity tradeoffs in the average sense. We illustrate this setup on the Quadratic Assignment Problem, a fundamental problem in Network Science. We observe that data-driven models based on Graph Neural Networks offer intriguingly good performance, even in regimes where standard relaxation based techniques appear to suffer.