Moving average quality control of routine chemistry and hematology parameters - a toolbox for implementation.

OBJECTIVES: Moving average quality control (MA QC) is a patient-based real-time quality control system. Advantages compared to conventional periodic internal quality control (IQC) include absence of commutability problems and continuous monitoring of performance. We implemented MA QC for multiple routine hematology and chemistry parameters. We describe the evaluation process and provide practical tools to aid MA QC implementation. METHODS: Nine parameters (serum sodium, calcium, bicarbonate and free thyroxine, hemoglobin [Hb], mean corpuscular volume, mean corpuscular hemoglobin concentration [MCHC], reticulocyte count and erythrocyte sedimentation rate [ESR]) were chosen for initial consideration. Using data extractions from the laboratory information system (LIS; General Laboratory Information Management System), evaluation of usefulness and optimization of MA QC settings was performed using bias detection curves. After this, MA QC settings were incorporated in our LIS for further evaluation and implementation in routine care. RESULTS: Three out of nine parameters (Hb, ESR, and sodium) were excluded from MA QC implementation due to high variation and technical issues in the LIS. For the six remaining parameters, MA QC showed added value to IQC and was therefore implemented in the LIS. For three parameters a direct MA alarm work-up method was set up, including newly developed built-in features in the LIS. For the other parameters, we identified MA utilization beyond real-time monitoring. CONCLUSIONS: Implementation of MA QC has added value for our laboratory setting. Additional utilization beyond real-time QC monitoring was identified. We find MA QC especially useful for trend monitoring, detection of small shifts after maintenance and inter-analyzer comparisons.

Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour.

The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.

Diagnostic methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments.

Invasive bilirubin measurements remain the gold standard for the diagnosis and treatment of infants with severe neonatal hyperbilirubinemia. The present paper describes different methods currently available to assess hyperbilirubinemia in newborn infants. Novel point-of-care bilirubin measurement methods, such as the BiliSpec and the Bilistick, would benefit many newborn infants, especially in low-income and middle-income countries where the access to costly multi-analyzer in vitro diagnostic instruments is limited. Total serum bilirubin test results should be accurate within permissible limits of measurement uncertainty to be fit for clinical purposes. This implies correct implementation of internationally endorsed reference measurement systems as well as participation in external quality assessment programs. Novel analytic methods may, apart from bilirubin, include the determination of bilirubin photoisomers and bilirubin oxidation products in blood and even in other biological matrices. IMPACT: Key message: Bilirubin measurements in blood remain the gold standard for diagnosis and treatment of severe neonatal hyperbilirubinemia (SNH). External quality assessment (EQA) plays an important role in revealing inaccuracies in diagnostic bilirubin measurements. What does this article add to the existing literature? We provide analytic performance data on total serum bilirubin (TSB) as measured during recent EQA surveys. We review novel diagnostic point-of-care (POC) bilirubin measurement methods and analytic methods for determining bilirubin levels in biological matrices other than blood. Impact: Manufacturers should make TSB test results traceable to the internationally endorsed total bilirubin reference measurement system and should ensure permissible limits of measurement uncertainty.

Screening methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments.

Severe neonatal hyperbilirubinemia (SNH) is a serious condition that occurs worldwide. Timely recognition with bilirubin determination is key in the management of SNH. Visual assessment of jaundice is unreliable. Fortunately, transcutaneous bilirubin measurement for screening newborn infants is routinely available in many hospitals and outpatient settings. Despite a few limitations, the use of transcutaneous devices facilitates early recognition and appropriate management of neonatal jaundice. Unfortunately, however, advanced and often costly screening modalities are not accessible to everyone, while there is an urgent need for inexpensive yet accurate instruments to assess total serum bilirubin (TSB). In the near future, novel icterometers, and in particular optical bilirubin estimates obtained with a smartphone camera and processed with a smartphone application (app), seem promising methods for screening for SNH. If proven reliable, these methods may empower outpatient health workers as well as parents at home to detect jaundice using a simple portable device. Successful implementation of ubiquitous bilirubin screening may contribute substantially to the reduction of the worldwide burden of SNH. The benefits of non-invasive bilirubin screening notwithstanding, any bilirubin determination obtained through non-invasive screening must be confirmed by a diagnostic method before treatment. IMPACT: Key message: Screening methods for neonatal hyperbilirubinemia facilitate early recognition and timely treatment of severe neonatal hyperbilirubinemia (SNH). Any bilirubin screening result obtained must be confirmed by a diagnostic method. What does this article add to the existing literature? Data on optical bilirubin estimation are summarized. Niche research strategies for prevention of SNH are presented. Impact: Transcutaneous screening for neonatal hyperbilirubinemia contributes to the prevention of SNH. A smartphone application with optical bilirubin estimation seems a promising low-cost screening method, especially in low-resource settings or at home.

Influence of seed layers on optical properties of aluminum in the UV range.

The potential of titanium and copper seed layers to enhance the optical properties of aluminum films for ultra-violet (UV) applications is analyzed. The seed layers significantly influence the initial layer growth of aluminum films. For the titanium-seeded aluminum, a surface roughness of 0.34 nm was observed. UV spectral reflectance measurements showed an average higher reflectivity of 4.8% for wavelengths from 120 nm to 200 nm for the aluminum film grown on the titanium seed layer. Furthermore, the titanium-seeded aluminum coatings were stable at an elevated temperature of 225°C and showed no increase in surface roughness or pinholes.

Topography and geology of Uranian mid-sized icy satellites in comparison with Saturnian and Plutonian satellites.

Newly processed global imaging and topographic mapping of Uranus's five major satellites reveal differences and similarities to mid-sized satellites at Saturn and Pluto. Three modes of internal heat redistribution are recognized. The broad similarity of Miranda's three oval resurfacing zones to those mapped on Enceladus and (subtly) on Dione are likely due to antipodal diapiric upwelling. Conversely, break-up and foundering of crustal blocks accompanied by extensive (cryo)volcanism is the dominant mode on both Charon and Ariel. Titania's fault network finds parallels on Rhea, Dione, Tethys and possibly Oberon. Differences in the geologic style of resurfacing in the satellite systems (e.g. plains on Charon, Dione, Tethys and perhaps Titania versus ridges on Miranda and Ariel) may be driven by differences in ice composition. Surface processes such as volatile transport may also be indicated by bright and dark materials on Oberon, Umbriel and Charon. The more complete and higher quality observations of the Saturnian and Plutonian mid-sized icy satellites by Cassini and New Horizons reveal a wealth of features and phenomena that cannot be perceived in the more limited Voyager coverage of the Uranian satellites, harbingers of many discoveries awaiting us on a return to Uranus. This article is part of a discussion meeting issue 'Future exploration of ice giant systems'.

Structure and evolution of the lunar Procellarum region as revealed by GRAIL gravity data.

The Procellarum region is a broad area on the nearside of the Moon that is characterized by low elevations, thin crust, and high surface concentrations of the heat-producing elements uranium, thorium, and potassium. The region has been interpreted as an ancient impact basin approximately 3,200 kilometres in diameter, although supporting evidence at the surface would have been largely obscured as a result of the great antiquity and poor preservation of any diagnostic features. Here we use data from the Gravity Recovery and Interior Laboratory (GRAIL) mission to examine the subsurface structure of Procellarum. The Bouguer gravity anomalies and gravity gradients reveal a pattern of narrow linear anomalies that border Procellarum and are interpreted to be the frozen remnants of lava-filled rifts and the underlying feeder dykes that served as the magma plumbing system for much of the nearside mare volcanism. The discontinuous surface structures that were earlier interpreted as remnants of an impact basin rim are shown in GRAIL data to be a part of this continuous set of border structures in a quasi-rectangular pattern with angular intersections, contrary to the expected circular or elliptical shape of an impact basin. The spatial pattern of magmatic-tectonic structures bounding Procellarum is consistent with their formation in response to thermal stresses produced by the differential cooling of the province relative to its surroundings, coupled with magmatic activity driven by the greater-than-average heat flux in the region.

Application of a point of care creatinine device for trend monitoring in kidney transplant patients: fit for purpose?

BACKGROUND: The StatSensor® Xpress-i™, a point-of-care system for blood creatinine measurement, offers patients the possibility of self-monitoring creatinine. In this study, the analytical performance of the StatSensor® for both detecting current renal function and monitoring renal (dys)function in kidney transplant patients was examined. METHODS: Accuracy of the StatSensor® with capillary and venous whole blood was evaluated and compared to an isotopic dilution mass spectrometry (IDMS)-traceable enzymatic creatinine test in venous serum (n=138). Twenty Li-heparin samples were compared to the IDMS reference method performed by a Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference laboratory (RfB, Bonn, Germany). To evaluate StatSensor®'s suitability to monitor kidney function, both venous and capillary samples were obtained in 20 hospitalized transplantation patients. Venous samples were analyzed with an IDMS-traceable enzymatic test, capillary samples were measured using the StatSensor®. For all 2-day intervals, percentage change in creatinine was compared between both methods. RESULTS: The StatSensor® did not meet total allowable error criterion of 6.9%. Average overall CVa for the StatSensor® was 10.4% and 5.2% for capillary and venous whole blood results, respectively. Overall CVa for the central laboratory serum creatinine method was <1.5%. For monitoring renal (dys)function, total agreement of the StatSensor® with an IDMS-traceable enzymatic test was 68% using a 10% Δ change. No significant differences were found between the changes observed by both methods. CONCLUSIONS: Capillary blood testing with the StatSensor® is not advisable for determining current renal function with a single creatinine measurement in kidney transplant patients, mainly due to excessive analytical imprecision. However, our results suggest that capillary blood testing with the StatSensor® can be used for daily trend monitoring of kidney function after renal transplantation.

True polar wander on Europa from global-scale small-circle depressions.

The tectonic patterns and stress history of Europa are exceedingly complex and many large-scale features remain unexplained. True polar wander, involving reorientation of Europa's floating outer ice shell about the tidal axis with Jupiter, has been proposed as a possible explanation for some of the features. This mechanism is possible if the icy shell is latitudinally variable in thickness and decoupled from the rocky interior. It would impose high stress levels on the shell, leading to predictable fracture patterns. No satisfactory match to global-scale features has hitherto been found for polar wander stress patterns. Here we describe broad arcuate troughs and depressions on Europa that do not fit other proposed stress mechanisms in their current position. Using imaging from three spacecraft, we have mapped two global-scale organized concentric antipodal sets of arcuate troughs up to hundreds of kilometres long and 300 m to approximately 1.5 km deep. An excellent match to these features is found with stresses caused by an episode of approximately 80 degrees true polar wander. These depressions also appear to be geographically related to other large-scale bright and dark lineaments, suggesting that many of Europa's tectonic patterns may also be related to true polar wander.

Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

Associations between ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles in relation to efavirenz and nevirapine pharmacokinetics in HIV-infected individuals.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals show large interindividual variation in response to antiretroviral therapy. Efavirenz (EFV) and nevirapine (NVP) are nonnucleoside reverse transcriptase inhibitors, which are prescribed in combination with other antiretroviral therapy in so-called highly active antiretroviral therapy. Recent studies provide evidence for the role of cytochrome P450 (CYP) genes, in particular CYP2B6, in relation to EFV and NVP pharmacokinetics. In this study, the authors investigated whether common ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles are associated with plasma concentrations of EFV and NVP in HIV-infected individuals. METHODS: Plasma drug concentrations were quantified by high-performance liquid chromatography in 143 HIV-infected individuals receiving either EFV or NVP. Genotyping for common alleles was performed by restriction fragment length polymorphism and Taqman assays. Individuals were genotyped for 11 single-nucleotide polymorphisms in 5 genes. CYP2B6 haplotypes were reconstructed by PHASE. RESULTS: Plasma EFV concentrations were positively associated with CYP2B6 c.516G>T, c.785A>G, and c.983A>G single-nucleotide polymorphisms in HIV-infected individuals. Increased plasma concentrations of EFV and NVP were present in individuals with the CYP2B6*6/*6 or *6/*18 haplotype compared with CYP2B6*1/*1 [increase of 62% (95% confidence interval, 44.0-80.1) and 24% (95% confidence interval, 7.0-40.0), respectively, P < 0.01]. No significant association with other genes in relation to EFV or NVP concentrations was found. CONCLUSIONS: In this study, a strong association of CYP2B6*6 and CYP2B6*18 alleles in relation to EFV and NVP plasma concentrations was found, which confirmed previous studies.

Large-scale cryovolcanic resurfacing on Pluto.

The New Horizons spacecraft returned images and compositional data showing that terrains on Pluto span a variety of ages, ranging from relatively ancient, heavily cratered areas to very young surfaces with few-to-no impact craters. One of the regions with very few impact craters is dominated by enormous rises with hummocky flanks. Similar features do not exist anywhere else in the imaged solar system. Here we analyze the geomorphology and composition of the features and conclude this region was resurfaced by cryovolcanic processes, of a type and scale so far unique to Pluto. Creation of this terrain requires multiple eruption sites and a large volume of material (>104 km3) to form what we propose are multiple, several-km-high domes, some of which merge to form more complex planforms. The existence of these massive features suggests Pluto's interior structure and evolution allows for either enhanced retention of heat or more heat overall than was anticipated before New Horizons, which permitted mobilization of water-ice-rich materials late in Pluto's history.

Planetary science: constant illumination at the lunar north pole.

Images returned by the spacecraft Clementine have been used to produce a quantitative illumination map of the north pole of the Moon, revealing the percentage of time that points on the surface are illuminated during the lunar day. We have used this map to identify areas that are constantly illuminated during a lunar day in summer and which may therefore be in permanent sunlight. All are located on the northern rim of Peary crater, close to the north pole. Permanently sunlit areas represent prime locations for lunar outpost sites as they have abundant solar energy, are relatively benign thermally (when compared with equatorial regions), and are close to permanently shadowed regions that may contain water ice.

Morphometric Study of Craters on Saturn's Moon Rhea.

Morphometric studies of impact craters on icy moons can be used to understand modification of crater topography. Several processes (e.g., viscous relaxation, ejecta deposition, repeated and overlapping impacts) act to shallow crater depth and relax the crater wall slope to similar or varying extents. Resolving these processes can help constrain the interior structure and surface properties of icy moons. Here, using morphometric measurements of craters on Rhea, we aim to constrain the processes that led to the observed crater population. We measured crater diameter, depth, and wall slope, as well as overall crater morphology (e.g., simple versus complex craters). Our results indicate that there exists a linear correlation between impact crater depth-to-diameter ratio and crater wall slope. This may suggest that the dominant modification process on Rhea is one that affects both properties simultaneously, which supports past heating events as the primary post-impact modification process. Additionally, the simple-to-complex crater transition for Rhea was found to be 12 ± 2 km, which is consistent with reported transition diameters for comparably sized icy bodies, indicating similar surface properties. A transition to shallower crater depths for large complex craters was not documented, indicating the absence of a rheological transition at depth in Rhea's icy lithosphere, which may support the interpretation that Rhea is not fully differentiated.

Effect of an electric field during the deposition of silicon dioxide thin films by plasma enhanced atomic layer deposition: an experimental and computational study.

The growth, chemical, structural, mechanical, and optical properties of oxide thin films deposited by plasma enhanced atomic layer deposition (PEALD) are strongly influenced by the average-bias voltage applied during the reaction step of surface functional groups with oxygen plasma species. Here, this effect is investigated thoroughly for SiO2 deposited in two different PEALD tools at average-bias voltages up to -300 V. Already at a very low average-bias voltage (< -10 V), the SiO2 films have significantly lower water content than films grown without biasing together with the formation of denser films having a higher refractive index and nearly stoichiometric composition. Substrate biasing during PEALD also enables control of mechanical stress. The experimental findings are supported by density functional theory and atomistic simulations. They demonstrate that the application of an electric field during the plasma step results in an increased energy transfer between energetic ions and the surface, directly influencing relevant surface reactions. Applying an electric field during the PEALD process leads to SiO2 thin films with significantly improved properties comparable to films grown by ion beam sputtering.

'Just breathe normally': word choices that trigger nocebo responses in patients.

Negative reactions to placebo medications -- sometimes called "nocebo effects" -- are well documented. Similar responses can be induced in suggestible patients when providers use language that tends to increase patients' stress and negative expectations. Several common "language traps" are examined and alternative ways to communicate with patients are suggested.