Nov 1, 1995; 18:1524-1525
Syst[egrave]me International (SI) Units

Rob M. van Dam
Dec 1, 2004; 27:2990-2992
Brief Reports

Aug 1, 1995; 18:1223-1224
Syst[egrave]me International (SI) Units

Michael Schweinberger, Jonathan Stewart.

Source: The Annals of Statistics, Volume 48, Number 1, 374--396.

Abstract:
Statistical inference for exponential-family models of random graphs with dependent edges is challenging. We stress the importance of additional structure and show that additional structure facilitates statistical inference. A simple example of a random graph with additional structure is a random graph with neighborhoods and local dependence within neighborhoods. We develop the first concentration and consistency results for maximum likelihood and $M$-estimators of a wide range of canonical and curved exponential-family models of random graphs with local dependence. All results are nonasymptotic and applicable to random graphs with finite populations of nodes, although asymptotic consistency results can be obtained as well. In addition, we show that additional structure can facilitate subgraph-to-graph estimation, and present concentration results for subgraph-to-graph estimators. As an application, we consider popular curved exponential-family models of random graphs, with local dependence induced by transitivity and parameter vectors whose dimensions depend on the number of nodes.

Gábor Lugosi, Shahar Mendelson, Nikita Zhivotovskiy.

Source: Bernoulli, Volume 26, Number 3, 2253--2274.

Abstract:
We present results on the concentration properties of the spectral norm $|A_{p}|$ of the adjacency matrix $A_{p}$ of an Erdős–Rényi random graph $G(n,p)$. First, we consider the Erdős–Rényi random graph process and prove that $|A_{p}|$ is uniformly concentrated over the range $pin[Clog n/n,1]$. The analysis is based on delocalization arguments, uniform laws of large numbers, together with the entropy method to prove concentration inequalities. As an application of our techniques, we prove sharp sub-Gaussian moment inequalities for $|A_{p}|$ for all $pin[clog^{3}n/n,1]$ that improve the general bounds of Alon, Krivelevich, and Vu ( Israel J. Math. 131 (2002) 259–267) and some of the more recent results of Erdős et al. ( Ann. Probab. 41 (2013) 2279–2375). Both results are consistent with the asymptotic result of Füredi and Komlós ( Combinatorica 1 (1981) 233–241) that holds for fixed $p$ as $n oinfty$.

Jing Lei.

Source: Bernoulli, Volume 26, Number 1, 767--798.

Abstract:
We provide upper bounds of the expected Wasserstein distance between a probability measure and its empirical version, generalizing recent results for finite dimensional Euclidean spaces and bounded functional spaces. Such a generalization can cover Euclidean spaces with large dimensionality, with the optimal dependence on the dimensionality. Our method also covers the important case of Gaussian processes in separable Hilbert spaces, with rate-optimal upper bounds for functional data distributions whose coordinates decay geometrically or polynomially. Moreover, our bounds of the expected value can be combined with mean-concentration results to yield improved exponential tail probability bounds for the Wasserstein error of empirical measures under Bernstein-type or log Sobolev-type conditions.

Maxim Rabinovich, Aaditya Ramdas, Michael I. Jordan, Martin J. Wainwright.

Source: Bayesian Analysis, Volume 15, Number 2, 505--532.

Abstract:
Slow mixing is the central hurdle is applications of Markov chains, especially those used for Monte Carlo approximations (MCMC). In the setting of Bayesian inference, it is often only of interest to estimate the stationary expectations of a small set of functions, and so the usual definition of mixing based on total variation convergence may be too conservative. Accordingly, we introduce function-specific analogs of mixing times and spectral gaps, and use them to prove Hoeffding-like function-specific concentration inequalities. These results show that it is possible for empirical expectations of functions to concentrate long before the underlying chain has mixed in the classical sense, and we show that the concentration rates we achieve are optimal up to constants. We use our techniques to derive confidence intervals that are sharper than those implied by both classical Markov-chain Hoeffding bounds and Berry-Esseen-corrected central limit theorem (CLT) bounds. For applications that require testing, rather than point estimation, we show similar improvements over recent sequential testing results for MCMC. We conclude by applying our framework to real-data examples of MCMC, providing evidence that our theory is both accurate and relevant to practice.

The Bradford assay is a quick and fairly sensitive method for measuring the concentrations of proteins. It is based on the shift in absorbance maximum of Coomassie Brilliant Blue G-250 dye from 465 to 595 nm following binding to denatured proteins in solution.

Determining the concentration of protein samples generally is accomplished either by measuring the UV absorbance at 280 nm or by reacting the protein quantitatively with dyes and/or metal ions (Bradford, Lowry, or BCA assays). For purified proteins, UV absorbance remains the most popular method because it is fast, convenient, and reproducible; it does not consume the protein; and it requires no additional reagents, standards, or incubations. No method of protein concentration determination is perfect because each is subject to a different set of constraints such as interference of buffer components and contaminating proteins in direct UV determination (A₂₈₀) or reactivity of individual proteins and buffer components with the detecting reagents in colorimetric assays. In cases in which protein concentration is critical (e.g., determination of catalytic rate constants for an enzyme), it may be advisable to compare the results of several assays.

Nearly one-third of all US children are overweight or obese, with even higher prevalence among Mexican American children. Overweight and obesity increase systemic inflammation, contributing to increased risk for chronic diseases, such as type 2 diabetes mellitus and cardiovascular disease.

Obese Mexican American children had concurrent alterations in both inflammatory markers and traditional disease risk markers, relative to healthy weight children. Our results provide evidence partially explaining the health disparity for disease in Mexican American children who are overweight/obese. (Read the full article)

There is no literature on the concentrations of vitamin B₆ vitamers in cerebrospinal fluid of preterm and term newborn infants. This knowledge, however, is highly important, because vitamin B₆ plays a pivotal role in brain development and functioning.

In cerebrospinal fluid of newborn infants, B₆ vitamer concentrations are strongly dependent on postmenstrual age, indicating that vitamin B₆ homeostasis in brain differs between preterm and term newborns. This has implications for the evaluation of epilepsy and vitamin B₆ deficiency. (Read the full article)

A serum 25-hydroxyvitamin D (25(OH)D) concentration of 20 ng/mL meets the requirements of at least 97.5% of the population older than 1 year. A recommended dietary intake to achieve this serum 25(OH)D concentration has not been established during infancy.

Daily maternal (during pregnancy) and then infant vitamin supplementation with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥20 ng/mL during infancy with the higher dose sustaining this increase for longer. (Read the full article)

Aspergillus niger, the third species responsible for invasive aspergillosis has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri. However little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The Minimum Inhibitory Concentrations (MICs) of itraconazole, voriconazole, posaconazole, isavuconazole and amphotericin B were determined by both the EUCAST and gradient concentration strips methods. Aspergillus tubingensis (n=51, 45.5%) and A. welwitschiae (n=50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n=7). The MICs of azoles drugs were higher for A. tubingensis than for A. welwitschiae. The MIC of amphotericin B was 2 mg/L or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by gradient concentration strips methods, these latter being lower than the former (Spearman's rank correlation tests ranging - depending on the antifungal agent - from 0.01 to 0.25; p>0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri. The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and gradient concentration strips methods require further investigation.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01-0.66 μg/ml) and micafungin levels (<0.01-0.16 μg/ml) were lower than the simultaneous plasma concentrations (0.77-5.07 μg/ml and 1.21-8.70 μg/ml, respectively). In cerebral cortex, anidulafungin and micafungin levels were 0.21-2.34 μg/g and 0.18-2.88 μg/g, respectively. Thus, MIC values of several pathogenic Candida strains exceed concentrations in CSF and in brain.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

Fredrik Christiansen, Kate R. Sprogis, Jasmin Gross, Juliana Castrillon, Hunter A. Warick, Eva Leunissen, and Susan Bengtson Nash

An animal's body condition provides valuable information for ecophysiological studies, and is an important measure of fitness in population monitoring and conservation. While both the external body shape of an animal and its internal tissues (i.e. fat content) can be used as a measure of body condition, the relationship between the two is not always linear. We compared the morphological body condition (external metric obtained through aerial photogrammetry) of migrating humpback whales (Megaptera novaeangliae) with their outer blubber lipid concentration (internal metric obtained through blubber biopsy sampling) off the coast of south-west Australia early and late in the breeding season (spanning ~4.5 months). The external body condition index of juvenile and adult humpback whales decreased by 26.9 (from 18.8% to –8.1%) and 12.0 percentage points (from 8.6% to –3.4%), respectively, between the early and late phase. In contrast, we found no intra-seasonal change in blubber lipid concentration, and no difference between reproductive classes (juveniles, adults and lactating females); however, the small sample size prevented us from effectively testing these effects. Importantly, however, in the 33 animals for which paired metrics were obtained, we found no correlation between the morphometric body condition index and the blubber lipid concentration of individual whales. The lack of a linear relationship suggests that changes in outer blubber lipid concentration do not reflect external changes in body shape, thus limiting the utility of outer blubber lipid reserves for individual body condition evaluation. The wider spectrum of change in body morphometry captured with aerial photogrammetry supports the use of body morphometry as a reliable and well-tested method.

Paclitaxel has been considered to cause OATP1B-mediated drug-drug interactions at therapeutic doses; however, its clinical relevance has not been demonstrated. This study aimed to elucidate in vivo inhibition potency of paclitaxel against OATP1B1 and OATP1B3 using endogenous OATP1B biomarkers. Paclitaxel is an inhibitor of OATP1B1 and OATP1B3, with K_i of 0.579 ± 0.107 and 5.29 ± 3.87 μM, respectively. Preincubation potentiated its inhibitory effect on both OATP1B1 and OATP1B3, with K_i of 0.154 ± 0.031 and 0.624 ± 0.183 μM, respectively. Ten patients with non–small cell lung cancer who received 200 mg/m² of paclitaxel by a 3-hour infusion were recruited. Plasma concentrations of 10 endogenous OATP1B biomarkers—namely, coproporphyrin I, coproporphyrin III, glycochenodeoxycholate-3-sulfate, glycochenodeoxycholate-3-glucuronide, glycodeoxycholate-3-sulfate, glycodeoxycholate-3-glucuronide, lithocholate-3-sulfate, glycolithocholate-3-sulfate, taurolithocholate-3-sulfate, and chenodeoxycholate-24-glucuronide—were determined in the patients with non–small cell lung cancer on the day before paclitaxel administration and after the end of paclitaxel infusion for 7 hours. Paclitaxel increased the area under the plasma concentration-time curve (AUC) of the endogenous biomarkers 2- to 4-fold, although a few patients did not show any increment in the AUC ratios of lithocholate-3-sulfate, glycolithocholate-3-sulfate, and taurolithocholate-3-sulfate. Therapeutic doses of paclitaxel for the treatment of non–small cell lung cancer (200 mg/m²) will cause significant OATP1B1 inhibition during and at the end of the infusion. This is the first demonstration that endogenous OATP1B biomarkers could serve as surrogate biomarkers in patients.

SIGNIFICANCE STATEMENT

Endogenous biomarkers can address practical and ethical issues in elucidating transporter-mediated drug-drug interaction (DDI) risks of anticancer drugs clinically. We could elucidate a significant increment of the plasma concentrations of endogenous OATP1B biomarkers after a 3-hour infusion (200 mg/m²) of paclitaxel, a time-dependent inhibitor of OATP1B, in patients with non–small cell lung cancer. The endogenous OATP1B biomarkers are useful to assess the possibility of OATP1B-mediated DDIs in patients and help in appropriately designing a dosing schedule to avoid the DDIs.

3-Mercaptopyruvate sulfur transferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate (3-MP) and transfers sulfane sulfur from an enzyme-bound persulfide intermediate to thiophilic acceptors such as thioredoxin and cysteine. Hydrogen sulfide (H2S), a signaling molecule implicated in many physiological processes, can be released from the persulfide product of the MPST reaction. Two splice variants of MPST, differing by 20 amino acids at the N terminus, give rise to the cytosolic MPST1 and mitochondrial MPST2 isoforms. Here, we characterized the poorly-studied MPST1 variant and demonstrated that substitutions in its Ser–His–Asp triad, proposed to serve a general acid–base role, minimally affect catalytic activity. We estimated the 3-MP concentration in murine liver, kidney, and brain tissues, finding that it ranges from 0.4 μmol·kg−1 in brain to 1.4 μmol·kg−1 in kidney. We also show that N-acetylcysteine, a widely-used antioxidant, is a poor substrate for MPST and is unlikely to function as a thiophilic acceptor. Thioredoxin exhibits substrate inhibition, increasing the KM for 3-MP ∼15-fold compared with other sulfur acceptors. Kinetic simulations at physiologically-relevant substrate concentrations predicted that the proportion of sulfur transfer to thioredoxin increases ∼3.5-fold as its concentration decreases from 10 to 1 μm, whereas the total MPST reaction rate increases ∼7-fold. The simulations also predicted that cysteine is a quantitatively-significant sulfane sulfur acceptor, revealing MPST's potential to generate low-molecular-weight persulfides. We conclude that the MPST1 and MPST2 isoforms are kinetically indistinguishable and that thioredoxin modulates the MPST-catalyzed reaction in a physiologically-relevant concentration range.

Clostridioides difficile infection (CDI) is one of the most common health care-associated infections that can cause significant morbidity and mortality. CDI diagnosis involves laboratory testing in conjunction with clinical assessment. The objective of this study was to assess the performance of various C. difficile tests and to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (C_T), and Singulex Clarity C. diff toxins A/B (Clarity) concentrations between groups with discordant test results. Unformed stool specimens from 200 hospitalized adults (100 PCR positive and 100 negative) were tested by cell cytotoxicity neutralization assay (CCNA), C. diff Quik Chek Complete (Quik Chek), Premier Toxins A and B, and Clarity. Clinical data, including CDI severity and CDI risk factors, were compared between discordant test results. Compared to CCNA, PCR had the highest sensitivity at 100% and Quik Chek had the highest specificity at 100%. Among clinical and laboratory data studied, prevalences of leukocytosis, prior antibiotic use, and hospitalizations were consistently higher across all subgroups in comparisons of toxin-positive to toxin-negative patients. Among PCR-positive samples, the median C_T was lower in toxin-positive samples than in toxin-negative samples; however, C_T ranges overlapped. Among Clarity-positive samples, the quantitative toxin concentration was significantly higher in toxin-positive samples than in toxin-negative samples as determined by CCNA and Quik Chek Toxin A and B. Laboratory tests for CDI vary in sensitivity and specificity. The quantitative toxin concentration may offer value in guiding CDI diagnosis and treatment. The presence of leukocytosis, prior antibiotic use, and previous hospitalizations may assist with CDI diagnosis, while other clinical parameters may not be consistently reliable.

S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts.Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events.Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P < 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P < 0.001 for linearity). Subgroup analyses further confirmed these associations.High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.

Mediterranean sediments are shown to have up to 1.9 million tiny plastic pieces per square metre.

The Department of Justice has initiated removal proceedings against a Sharon, Penn., resident who served as an armed SS guard at two Nazi concentration camps in Germany during World War II.

An immigration judge in Philadelphia has ordered the removal of Anton Geiser, a resident of Sharon, Pa., who served as an armed SS guard at three Nazi concentration camps in Germany during World War II.

Teen aristocrat Charles William Llewellyn Cadogan (pictured left with his father), 19, was driving his grey BMW at 71mph in a 50mph zone near his family's castle in Perth when he was pulled over.

The headlines will have made painful reading for Stuart Hogg yesterday after his costly howler in Dublin, but I thought he fronted up well afterwards and stayed focused during the game.

Heather Scott, left, was speaking after Governor Brad Little, right, extended statewide lockdowns until the end of April. Scott said calling businesses 'non essential' is 'no different than Nazi Germany'

Researchers from Poland's Institute of National Remembrance pieced together the layout of the Preventive Security Police Camp for Polish Youth in Lodz, where hundreds of children died.

Eliezer Grynfeld (pictured) died in Israel last week, leaving two children, five grandchildren and six great-grandchildren.

Hazlewood even said that he might consider Mankading Pujara the next time the two sides face each other in a Test series.

Barker Library - TA357.5.M43 L37 2013

Cham : Springer International Publishing : Imprint: Springer, 2014