bluuebunny/crossref_metadata_2025 huggingface dataset:
The grammaticalisation of verb-auxiliary order in East African Bantu
Authors: Gibson Hannah
Published: January 2020

Bantu languages employ a combination of simple and compound verb forms to encode tense-aspect-mood distinctions. Compound constructions typically involve an auxiliary form followed by an inflected main verb. However, the six East African Bantu languages under examination in this paper exhibit a word order in which the auxiliary appears after the verb. This order is typologically unusual for languages with SVO word order and comparatively unusual in the context of the Bantu languages. This paper presents a synchronic description of this word order and develops an account of its possible origins. It is proposed that the verb-auxiliary order originated from a verb-fronting construction which was used historically to convey predication focus. The account further corroborates the claim that the progressive aspect is an inherently focal category in Bantu and, from a wider perspective, shows the interplay between the encoding of information structure and tense-aspect information.
Neuronal GDPGP1 and glycogen metabolism: friend or foe?
Authors: Singhal Neel S. , Lee Evan M. , Ma Dengke K.
Published: January 2020

The adult brain consumes glucose for energy needs and stores glucose as glycogen mainly in astrocytes. Schulz et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201807127) identify the stress-regulated metabolic enzyme GDPGP1 that promotes neuronal survival likely through glycogen reserves in mouse and C. elegans neurons.
Susana Godinho: Placing cell biology at the center of cancer research
Authors: O’Donnell Marie Anne
Published: January 2020

Godinho investigates the role centrosomes play in cancer cell biology.
3. Arrogance: March 1867– May 1868
Authors: Guelzo Allen C.
Published: January 2020

For the survivors of the defeated Confederacy, the first issue was simple survival. The war had wrecked the Southern economy with total direct and indirect costs of the war for the South estimated as close to $13.6 billion. ‘Arrogance, March 1867–May 1868’ describes the victorious Northerners push for free labor to support the new economy, as well as the Southerners struggle to accept changing attitudes to their former slaves. Four Reconstruction bills were passed between February 1867 and March 1868, but Andrew Johnson used his military authority to undermine them. An attempt to impeach the president in May 1868 ultimately failed.
6. Law: 1866–1876
Authors: Guelzo Allen C.
Published: January 2020

So much of Reconstruction is understood as a struggle over race, politics, and the nature of state sovereignty within a federal system that not enough attention is paid to how it was also a constitutional struggle between the branches of the federal government. ‘Law, 1866–876’ describes the key legal debates that were raised during the presidencies of Abraham Lincoln, Andrew Johnson, and Ulysses S. Grant. The U.S. Constitution apportioned various federal responsibilities among the three federal branches—executive (the presidency), legislative (Congress), and judicial (the federal courts)—but it did not do so evenly or in the same detail.
3. Constructing Judaism and Christianity (70 ce–1054 ce)
Authors: Cohen Charles L.
Published: January 2020

“Constructing Judaism and Christianity (70 CE–1054 CE)” looks at how as Christians felt they now had to work to put form to their religion and its institutions, Jews were faced with the task of refashioning theirs. After the Temple’s destruction in 70 ce, Jews had to replace the observances and cult that had depended on its existence, investing legitimacy in new spaces, practices, leaders, and methods of textual interpretation. Christians were similarly trying to systematize their own scriptures, theology, and ecclesiastical organization. These identity constructions took shape as each group sought to distinguish itself from the others and their political fortunes shifted. Christianity’s elevation within the Roman Empire connected the faith to state power in ways that would inform the statement of its core theological premises, amplify divisions within the Church, and configure the course of Jewish–Christian relations.
7. Modern encounters (1500–2010)
Authors: Cohen Charles L.
Published: January 2020

“Modern encounters (1500–2010)” considers what happened after 1500 as Christianity became the preeminent religion in many of the world’s most powerful nations. This new power facilitated its global spread. After 1500, Christianity became the preeminent religion in many of the world’s most powerful nations, facilitating its global spread. The recovery of political sovereignty by Muslims in Asia and Africa following decolonization in the twentieth century resulted in reassertions of Islam’s foundational importance for their political cultures. Meanwhile, world Jewry reorganized itself primarily in Israel and the United States, the latter being a state that officially promoted no religion while proclaiming itself to be culturally Christian yet also committed to protecting religious liberty. As disagreements between Jews, Christians, and Muslims continued, some sought to improve relationships among them by launching global theological initiatives.
Epilogue
Authors: Cohen Charles L.
Published: January 2020

The epilogue critiques this proposition by examining two of the ways in which Judaism, Christianity, and Islam have historically colored their adherents’ experiences: as individuals who may have an intimate connection to God; and as communities defined by their collective heritages. Historical circumstances have colored how members of the Abrahamic religions see one another; so, too, have the ways in which their traditions have constructed their identities. Ruminating on the perceived connections between the traditions that the concept of the “Abrahamic religions” implies, proponents of interfaith engagement have sometimes fastened on Abraham as a model of how his self-proclaimed descendants might treat each other more generously.
Trigonometry: A Very Short Introduction
Authors: Van Brummelen Glen
Published: January 2020

Trigonometry: A Very Short Introduction draws together the full history of trigonometry, stretching across two millennia and several cultures such as ancient Greece, medieval India, and the Islamic world. It introduces the key concepts of trigonometry, drawing readers beyond the basic relationships first encountered in school to reveal the richness of the entire subject of trigonometry and ideas such as curved space. It also explores connections with genuine modern applications, including navigation, the analysis of music, computer graphics, and powerful modelling tools in science, and shows how trigonometry has participated in big questions about the world, including the shape of the universe and the nature of infinity.
4. Identities, and more identities
Authors: Van Brummelen Glen
Published: January 2020

The world of trigonometry is full of identities: some of them extremely useful, others beautiful, and a few that are simply bizarre. ‘Identities, and more identities’ takes a tour of the menagerie of identities, viewing a little from each of these categories. The first two examples are known as triangle identities, because they refer to angles and lengths in a given triangle. The Law of Sines and the Law of Cosines are discussed, along with Mollweide’s formulas, the Law of Tangents, Morrie’s Law, and the introduction of logarithms, which became the preferred computing tool in mathematical astronomy, and then in practical disciplines like surveying and architecture in the early 17th century.
5. To infinity …
Authors: Van Brummelen Glen
Published: January 2020

‘To infinity … ’ looks at how infinite trigonometric series are used to compute π. It shows how Machin’s formula used the inverse tangent series to compute π to a hundred places. Lord Kelvin’s use of Fourier analysis in studying tide behaviour is also explained along with the Gibbs phenomenon. The invention of Cartesian coordinates and calculus in the 17th and 18th centuries reflects a major shift in mathematics. Geometry gradually changed from being synthetic (in the style of Euclid) to being analytic. The basic mathematical objects―originally points, lines, and shapes as well as numbers―became functions that accept input quantities and produce output quantities.
7. Spheres and more
Authors: Van Brummelen Glen
Published: January 2020

‘Spheres and more’ considers the ten formulas for right-angled spherical triangles (and how they can be generated), the spherical Pythagorean theorem, and Napier’s rules. Spherical trigonometry was intended originally for astronomers, but medieval Islamic scholars used it to predict the beginning of the sacred month of Ramadan and the times of the five daily prayers. The impact of spherical geometry on Euclid’s axioms resulting in two types of non-Euclidean geometries—elliptical geometry and hyperbolic geometry—is also considered.
Niels Bohr: A Very Short Introduction
Authors: Heilbron J. L.
Published: January 2020

Niels Bohr: A Very Short Introduction covers the life and work of the pioneer of the quantum theory of the atom who ranks with Einstein in importance for the development of modern physics. In addition to his role as a scientist, Bohr was a statesman and Danish cultural icon, who built scientific institutions and pushed for the extension of international cooperation to all nation states. He also had deep interests in philosophy, literature, and humanism. This VSI considers how all of these aspects of Bohr’s personality influenced his ground-breaking work.
3. Magic wand
Authors: Heilbron J. L.
Published: January 2020

‘Magic wand’ refers to the ‘correspondence principle’ that Bohr devised and deployed to investigate the interface between quantum and ordinary (‘classical’) physics. The chapter covers various lines of work, some inspired by his approach and some independent of it, all of which confirmed its fertility. The mobilization of the international brotherhood of physicists for the Great War gave Bohr breathing space to develop the correspondence principle with the help of Hendrik Kramers, who had come to neutral Denmark to study with him, and in friendly competition with Arnold Sommerfeld, who made important formal extensions of the theory.
Korea: A Very Short Introduction
Authors: Seth Michael J.
Published: January 2020

Having spent centuries in the shadows of its neighbours China and Japan, Korea is now the object of considerable interest. Korea: A Very Short Introduction explores the history, culture, and society of a deeply divided region. It considers what it means to be Korean, and analyses how the various peoples of the Korean peninsula became one of the world’s most homogeneous nations, before exploring how this nation evolved, in a single lifetime, into today’s sharply contrasting societies of North Korea and South Korea. It also discusses how Korea fits into the larger narrative of both East Asian and world history, economically, politically, and socially.
3. From kingdom to colony
Authors: Seth Michael J.
Published: January 2020

‘From kingdom to colony’ explains that in the late 19th and early 20th centuries Korea became exposed to the new Western-dominated world of modern imperialism. The political and social order was seriously challenged, and the very existence of the state was threatened. Koreans responded by carrying out reforms and rethinking their ideas about their society and its place in the world. Despite their efforts at meeting the challenges it faced, their country fell under Japanese rule. With their limited connections to the world outside East Asia, Koreans were unprepared for the intrusion of modern imperialism, but they adjusted to the technological, institutional, and intellectual challenges of modernization, and an intense, passionate nationalism emerged.
6. Globalizing south, inward north
Authors: Seth Michael J.
Published: January 2020

‘Globalizing south, inward north’ shows that from the 1980s the two Koreas grew further apart, economically, politically, and culturally. Few states moved faster from poverty to ‘developed’ status than South Korea, none developed a more totalitarian, isolated society than North Korea. South Korea’s economy expanded impressively well into the 2000s, becoming a wealthy consumer society, while North Korea went through economic stagnation and decline. Both started with authoritarian political systems; however, the South evolved into an open, democratic society while the North remained authoritarian and closed. Most Koreans continued to see themselves as part of one nation united by common ethnicity and ancestry, and regarded the political division as unnatural and unacceptable. Is reunification possible?
1. What is art history?
Authors: Arnold Dana
Published: January 2020

‘What is art history?’ discusses the term art history and draws distinctions between it and art appreciation and art criticism. It also considers the range of artefacts included in the discipline and how these have changed over time. The work of art is our primary evidence, and it is our interaction between this evidence and methods of enquiry that forms art history. Art appreciation and criticism are also linked to connoisseurship. Although art is a visual subject, we learn about it through reading and we convey our ideas about it mostly in writing. The social and cultural issues articulated by art history are examined through an analysis of four very different works of art.
2. Writing art history
Authors: Arnold Dana
Published: January 2020

‘Writing art history’ looks at how histories of art have been written in Europe and North America and the effect that this has had on the object itself and on the subjects of art history. Discussing the work of influential art historians Pliny the Elder, Giorgio Vasari, Johann Joachim Winckelmann, Jacob Burckhardt, Ernst Gombrich, and Clement Greenberg, it introduces the expectations we have of art history as a chronological story about great Western male artists. Complementary to this gender bias is the impact of the writing of women art historians such as Griselda Pollock and Linda Nochlin. They have mapped out a different way of seeing and understanding cultural production and the social relationships expressed therein.
3. A global art history?
Authors: Arnold Dana
Published: January 2020

Are the practices of Western art history appropriate for the study of art from cultures outside its geographical boundaries and conventional timeframe? The bias in this interpretation of the subject opens up the questions of the importance of the canon in art history and how we view non-figurative, primitive, and naive art. ‘A global art history?’ considers a range of different examples of artistic practice from around the world, including the sculpture of the Dogon people of Mali and the calligraphy of Wu Zhen, who was active during the Yuan Dynasty (1271–1368). It also discusses what is meant by the ‘primitive’ arts of Oceania, Africa, and North and South America.
6. Reading art
Authors: Arnold Dana
Published: January 2020

‘Reading art’ discusses the idea of meaning in art, in particular of the quality and kinds of representation, and the use of iconography, or symbolism, in artworks throughout history. Focusing on figurative representation of the human form, it introduces some ways in which artworks themselves can be the starting point for how we read art history. Subject matter, materials, and methods combine in the process of reading art. A combination of different ways of writing, presenting, and thinking about art history converges on the works themselves to show how important it is to not lose sight of these objects and how art can indeed have a history.
Lung Asbestos Fibre Burden and Pleural Mesothelioma in Women with Non-occupational Exposure
Authors: Barbieri Pietro Gino , Somigliana Anna , Chen Yao , Consonni Dario , Vignola Roberto , Finotto Luigi
Published: January 2020

Background

Malignant pleural mesothelioma (MPM) due to environmental and familial (domestic) asbestos exposure is well recognized. However, information on cumulative asbestos dose in subjects affected by MPM is limited.

Objectives

To evaluate the residual lung asbestos fibre and asbestos body burden in women with MPM with past environmental and/or familial asbestos exposure.

Methods

We collected lung samples from autopsies regarding 15 non-occupationally asbestos-exposed MPM cases, divided in three groups: (i) familial exposure from the Fincantieri shipyards in Monfalcone (No. 7), (ii) environmental and familial asbestos exposure from the asbestos-cement plant Fibronit in Broni (No. 6), and (iii) environmental exposure from the Fibronit plant (No. 2). Asbestos body (AB) and fibres (AF) per gram of dry lung tissue were counted by optical and scanning electron microscopy, respectively, and expressed as geometric means and standard deviations (GM, GSD).

Results

GM/GSD of AB counts were 6123/9.6 (Group 1), 13 800/10.4 (Group 2), and 8400/1.1 (Group 3); GM/GSD of AF were 0.6/2.1 (Group 1), 7.9/2.1 (Group 2), and 6.0/2.3 (Group 3) million. Pleural plaques were observed in 12 cases.

Conclusions

Exclusive familial exposure to asbestos determined cumulative doses close to those observed in moderate occupational exposure circumstances. Our results also suggest that combined environmental and familial exposures may cause unexpectedly high cumulative fibre doses.
Prognosis for patients with cognitive motor dissociation identified by brain-computer interface
Authors: Pan Jiahui , Xie Qiuyou , Qin Pengmin , Chen Yan , He Yanbin , Huang Haiyun , Wang Fei , Ni Xiaoxiao , Cichocki Andrzej , Yu Ronghao , Li Yuanqing
Published: January 2020

Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients’ behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.
Dissociation between frontal and temporal-parietal contributions to connected speech in acute stroke
Authors: Ding Junhua , Martin Randi C , Hamilton A Cris , Schnur Tatiana T
Published: January 2020

Humans are uniquely able to retrieve and combine words into syntactic structure to produce connected speech. Previous identification of focal brain regions necessary for production focused primarily on associations with the content produced by speakers with chronic stroke, where function may have shifted to other regions after reorganization occurred. Here, we relate patterns of brain damage with deficits to the content and structure of spontaneous connected speech in 52 speakers during the acute stage of a left hemisphere stroke. Multivariate lesion behaviour mapping demonstrated that damage to temporal-parietal regions impacted the ability to retrieve words and produce them within increasingly complex combinations. Damage primarily to inferior frontal cortex affected the production of syntactically accurate structure. In contrast to previous work, functional-anatomical dissociations did not depend on lesion size likely because acute lesions were smaller than typically found in chronic stroke. These results are consistent with predictions from theoretical models based primarily on evidence from language comprehension and highlight the importance of investigating individual differences in brain-language relationships in speakers with acute stroke.
Metabolic lesion-deficit mapping of human cognition
Authors: Jha Ashwani , Teotonio Rute , Smith April-Louise , Bomanji Jamshed , Dickson John , Diehl Beate , Duncan John S , Nachev Parashkev
Published: January 2020

In theory the most powerful technique for functional localization in cognitive neuroscience, lesion-deficit mapping is in practice distorted by unmodelled network disconnections and strong ‘parasitic’ dependencies between collaterally damaged ischaemic areas. High-dimensional multivariate modelling can overcome these defects, but only at the cost of commonly impracticable data scales. Here we develop lesion-deficit mapping with metabolic lesions—discrete areas of hypometabolism typically seen on interictal 18F-fluorodeoxyglucose PET imaging in patients with focal epilepsy—that inherently capture disconnection effects, and whose structural dependence patterns are sufficiently benign to allow the derivation of robust functional anatomical maps with modest data. In this cross-sectional study of 159 patients with widely distributed focal cortical impairments, we derive lesion-deficit maps of a broad range of psychological subdomains underlying affect and cognition. We demonstrate the potential clinical utility of the approach in guiding therapeutic resection for focal epilepsy or other neurosurgical indications by applying high-dimensional modelling to predict out-of-sample verbal IQ and depression from cortical metabolism alone.
Reduced Modulation of Task-Related Connectivity Mediates Age-Related Declines in Bimanual Performance
Authors: Monteiro Thiago Santos , Zivari Adab Hamed , Chalavi Sima , Gooijers Jolien , King Brad (Bradley) Ross , Cuypers Koen , Mantini Dante , Swinnen Stephan Patrick
Published: January 2020

Aging is accompanied by marked changes in motor behavior and its neural correlates. At the behavioral level, age-related declines in motor performance manifest, for example, as a reduced capacity to inhibit interference between hands during bimanual movements, particularly when task complexity increases. At the neural level, aging is associated with reduced differentiation between distinct functional systems. Functional connectivity (FC) dedifferentiation is characterized by more homogeneous connectivity patterns across various tasks or task conditions, reflecting a reduced ability of the aging adult to modulate brain activity according to changing task demands. It is currently unknown, however, how whole-brain dedifferentiation interacts with increasing task complexity. In the present study, we investigated age- and task-related FC in a group of 96 human adults across a wide age range (19.9–74.5 years of age) during the performance of a bimanual coordination task of varying complexity. Our findings indicated stronger task complexity-related differentiation between visuomotor- and nonvisuomotor-related networks, though modulation capability decreased with increasing age. Decreased FC modulation mediated larger complexity-related increases in between-hand interference, reflective of worse bimanual coordination. Thus, the ability to maintain high motor performance levels in older adults is related to the capability to properly segregate and modulate functional networks.
Mortality, Human Immunodeficiency Virus (HIV) Transmission, and Growth in Children Exposed to HIV in Rural Zimbabwe
Authors: Evans Ceri , Chasekwa Bernard , Ntozini Robert , Majo Florence D , Mutasa Kuda , Tavengwa Naume , Mutasa Batsirai , Mbuya Mduduzi N N , Smith Laura E , Stoltzfus Rebecca J , Moulton Lawrence H , Humphrey Jean H , Prendergast Andrew J ,   for the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team
Published: January 2020

Background

Clinical outcomes of children who are human immunodeficiency virus (HIV)–exposed in sub-Saharan Africa remain uncertain.

Methods

The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial evaluated improved infant and young child feeding (IYCF) and/or improved water, sanitation, and hygiene in 2 rural Zimbabwean districts with 15% antenatal HIV prevalence and > 80% prevention of mother-to-child transmission (PMTCT) coverage. Children born between February 2013 and December 2015 had longitudinal HIV testing and anthropometry. We compared mortality and growth between children who were HIV-exposed and HIV-unexposed through 18 months. Children receiving IYCF were excluded from growth analyses.

Results

Fifty-one of 738 (7%) children who were HIV-exposed and 198 of 3989 (5%) children who were HIV-unexposed (CHU) died (hazard ratio, 1.41 [95% confidence interval {CI}, 1.02–1.93]). Twenty-five (3%) children who were HIV-exposed tested HIV positive, 596 (81%) were HIV-exposed uninfected (CHEU), and 117 (16%) had unknown HIV status by 18 months; overall transmission estimates were 4.3%–7.7%. Mean length-for-age z score at 18 months was 0.38 (95% CI, .24–.51) standard deviations lower among CHEU compared to CHU. Among 367 children exposed to HIV in non-IYCF arms, 147 (40%) were alive, HIV-free, and nonstunted at 18 months, compared to 1169 of 1956 (60%) CHU (absolute difference, 20% [95% CI, 15%–26%]).

Conclusions

In rural Zimbabwe, mortality remains 40% higher among children exposed to HIV, vertical transmission exceeds elimination targets, and half of CHEU are stunted. We propose the composite outcome of “alive, HIV free, and thriving” as the long-term goal of PMTCT programs.

Clinical Trials Registration

NCT01824940.
Measurement of strontium in serum, urine, bone, and soft tissues by Zeeman atomic absorption spectrometry
Authors: D’Haese Patrick C , Van Landeghem Glen F , Lamberts Ludwig V , Bekaert Vera A , Schrooten Iris , De Broe Marc E
Published: January 2020

To study the possible accumulation of Sr in chronic renal failure patients, methods were developed for the determination of the element in serum, urine, bone, and soft tissues by using Zeeman atomic absorption spectrometry. Serum samples were diluted 1:4 with a Triton X-100–HNO3 mixture, whereas urine samples were diluted 1:20 with HNO3. Bone samples were digested with concentrated HNO3 in stoppered polytetrafluoroethylene (Teflon®) tubes, whereas soft tissues were dissolved in a tetramethylammonium hydroxide solution in water. For serum and urine we used matrix-matched calibration curves, whereas bone and tissue samples were measured against aqueous calibrators. Atomization was performed from the wall of pyrolytically coated graphite tubes for all of the matrices under study. Both inter- and intraassay CVs were <6% (n = 12, n = 10, respectively), and the recovery of added analyte was close to 100% for all of the biological matrices under study. Detection limits were 1.2 μg/L (serum), 0.3 μg/L (urine), 0.4 μg/g (bone), and 2.2 ng/g (soft tissues), whereas the sensitivity determined by the slope of the calibration curve, i.e., the amount of Sr producing a 0.0044 integrated absorbance change in signal, was 2.4 pg, 2.4 pg, 3.9 pg, and 2.6 pg for these matrices respectively. We conclude that the present methods are precise and accurate and easily applicable for both routine use and research investigations. They will allow us to study the metabolism of the element in chronic renal failure patients and shed some light on the association that was recently noted between increased bone Sr concentrations and the development of osteomalacia in these individuals.
Short-term and long-term variability of plasma homocysteine measurement
Authors: Garg Uttam C , Zheng Zhi-Jie , Folsom Aaron R , Moyer Yvonne S , Tsai Michael Y , McGovern Paul , Eckfeldt John H
Published: January 2020

Within-person and methodological variability of a given analyte are important elements in determining whether an individual has altered concentrations of that analyte. We report the short-term (1 month) within-person, between-person, and methodological variability of plasma homocysteine in 20 healthy participants from whom samples were drawn weekly for 4 weeks. The short-term between-person variance was high, whereas within-person and methodological variances were relatively very low, giving a high reliability coefficient (R) for homocysteine (R = 0.94). The long-term (30 months) reliability coefficient was 0.65, but was greatly influenced by an outlier (R = 0.82 with the outlier excluded). The data suggest that an individual’s plasma homocysteine concentration is relatively constant over at least 1 month, and a single measurement characterizes the average concentration reasonably well.
Assessing fluid and electrolyte status in the newborn
Authors: Lorenz John M
Published: January 2020

Fluid and electrolyte assessment during the first week of life is complicated by rapid changes in fluid and electrolyte balance during the transition from fetal to neonatal life and by the newborn’s small size. A physiologic decrease in extracellular water volume, as well as a transient increase in serum potassium and transient decreases in plasma glucose and total plasma ionized calcium concentrations must be taken into account. In general, the more immature the newborn, the greater the changes that can be expected. The use of plasma creatinine as an indicator of glomerular filtration rate is limited because it is a function of maternal renal function at birth and because of non-steady-state conditions in the immediate postnatal period. Guidelines for monitoring schedules are provided on the basis of these physiologic considerations and the author’s experience. Method of blood sampling and time to separation of serum are important considerations in interpreting results. Minimization of sample volume is critical to minimize blood transfusion requirements. Clinicians should be aware of the analytical error associated with these measurements in their own institutions. Reference ranges are provided.
Detection of intrauterine illicit drug exposure by newborn drug testing
Authors: Kwong Tai C , Ryan Rita M
Published: January 2020

Identification of intrauterine drug-exposed newborns with toxicological screening may have benefits including close follow-up of the infant by both medical and social services. Applying specific written guidelines to select newborns for drug testing decreases bias and protects the physicians and hospitals involved. All drugs reported as positive should be confirmed by an appropriate second test. Urine and meconium testing are the best current options for identifying drug-exposed neonates. Urine testing sensitivity is low because of problems encountered in urine collections and the high thresholds used in current urine assays. The disadvantage to meconium testing is the increased labor and time required to work with this material. Testing of newborn hair is unlikely to be widely used until technically less demanding assays become available. Testing of amniotic fluid or gastric lavage is still in the developmental stages. Adopting lower urine assay thresholds for newborn samples would increase sensitivity and would be an appropriate modification of current methodologies.
Determination of xylosyltransferase activity in serum with recombinant human bikunin as acceptor
Authors: Weilke Christian , Brinkmann Thomas , Kleesiek Knut
Published: January 2020

Xylosyltransferase (XT) is the chain-initiating enzyme of the biosynthesis of chondroitin sulfate. So far, XT activity has been detected by incorporation of [14C]xylose in chemically deglycosylated cartilage proteoglycan or silk fibroin. However, these acceptors allow no reliable determination in blood. We found that recombinant bikunin is an excellent acceptor for XT. The Michaelis–Menten constants for the xylosylation of silk, deglycosylated cartilage proteoglycans, and bikunin were 545, 155, and 0.9 μmol/L, respectively. With recombinant bikunin as acceptor, we developed a sensitive assay that allows a precise determination of XT activity in serum. We measured the serum XT activities of 500 blood donors and observed a considerable sex and age dependence. XT activities in men (0.77–1.50 mU/L) were ∼30% higher than in women (0.58–1.20 mU/L) and reached a maximum in donors of ∼40 years of age. During the menstrual cycle, serum XT activity showed a significant coincidence with the β-estradiol concentration, and in the first trimester of pregnancy we observed a strong increase in serum XT activity.
Comparability of a new turbidimetric digoxin test with other immunochemical tests and with HPLC—a multicenter evaluation
Authors: Scholer André , Boecker Jörg , Engelmayer Ulf , Feldmann Knut , Hannak Dieter , Kattermann Reinhard , Oellerich Michael , Raith Hannelore , Schlebusch Harald , Wieland Heinrich , Willems Dominique , Jarausch Jochen , Domke Ingrid
Published: January 2020

A new turbidimetric inhibition immunoassay for digoxin (Tina-quant® □a Digoxin, Boehringer Mannheim) was evaluated in seven laboratories. It can be performed without sample pretreatment with ready-to-use reagents on nondedicated analyzers in combination with routine clinical chemistry. The studies revealed a good analytical performance: lower limit of detection 0.12 μg/L (3 SD from mean of blank); linearity up to 7.5 μg/L; median between-run CVs 8.1% (0.6 μg/L), 2.8% (1.5 μg/L), 1.9% (3 μg/L); mean analytical recovery in control sera 98–102%; slopes from 0.97 to 1.09 and intercepts from −0.28 to 0.10 μg/L in comparison with four immunoassays; and a high resistance to common interferents. The test was more resistant to digoxin-like immunoreactive factor (DLIF) interference than other methods, showing cross-reactivity only in some intensive care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant women, patients with renal failure, newborns), 90% of results were ≤0.26 μg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low reactivity. An interlaboratory survey revealed a good comparability of the Tina-quant □a test with the median of all methods (slope 0.99, intercept −0.06 μg/L). An HPLC method for digoxin based on isocratic separation of samples on an RP-18 column followed by detection by an immunoassay yielded a reasonable comparability with the immunochemical tests with noncritical samples. Divergent results of immunoassays caused by DLIFs or different cross-reactivities with digoxin metabolites or derivatives can be explained by the use of this HPLC method.
Combinations of β chain abnormal hemoglobins with each other or with β-thalassemia determinants with known mutations: influence on phenotype
Authors: Huisman Titus Hendrik Jan
Published: January 2020

Hematological and hemoglobin (Hb) data are presented for numerous patients with compound heterozygosities for different β chain variants and for a β chain variant with different β-thalassemia (β-thal) alleles. Considerable variations, which result from the type of β chain variant and β-thal mutation, can be noted. The comparison again emphasizes the importance of determining the diagnoses at the molecular level to aid the physician in the management of patients with different combinations of abnormalities. Simplification and commercialization of modern technology may make the introduction of this approach in some clinical chemistry laboratories possible.
Multicenter evaluation of a second-generation assay for cardiac troponin T
Authors: Baum Hannsjörg , Braun Siegmund , Gerhardt Willie , Gilson Georges , Hafner Gerd , Müller-Bardorff Margit , Stein Wolfgang , Klein Gerhard , Ebert Christoph , Hallermayer Klaus , Katus Hugo A
Published: January 2020

We report on the evaluation of the second-generation assay for cardiac troponin T (cTnT) on the Enzymun®system. This new assay is completely specific for the cardiac isoform of TnT, utilizing two cardiospecific monoclonal antibodies. The assay time is reduced to 45 min. The interassay precision shows a median CV of 5.5%; 20% interassay CV was found between 0.05 and 0.1 μg/L. The cardiosensitivity of the second-generation cTnT assay in patients with ischemic myocardial injury appears equivalent when compared with the first-generation assay. We found no falsely positive results in patients with skeletal muscle damage including multitraumas, surgery patients, and marathon runners who showed highly increased values with the unspecific first-generation assay. In Duchenne disease cTnT was still increased, but to a much lower extent. cTnT remains increased in renal failure, but to a lesser degree than with the first-generation assay. The cause of this increase remains unclear. Although a cross-reactivity of skeletal muscle TnT in the second-generation assay could be excluded by our findings, minor myocardial damage or expression of the cardiac isoform of TnT in regenerating muscles cannot be ruled out in those cases with apparently falsely increased cTnT values. The second-generation cTnT assay is a step forward in the combination of cardiosensitivity and cardiospecificity in biochemical markers for diagnosis of heart disease.
Evaluation of precipitation and direct methods for HDL-cholesterol assay by HPLC
Authors: Okazaki Mitsuyo , Sasamoto Keiko , Muramatsu Toshio , Hosaki Seijin
Published: January 2020

HDL-cholesterol (HDL-C) values measured by precipitation (sodium phosphotungstate–MgCl2) and direct methods were compared with those obtained by HPLC with a new column (TSKgel Lipopropak) and an eluent (TSKeluent LP-1). The HDL-C values determined by the precipitation method were significantly (P <0.001) lower than those by the HPLC method, whereas the HDL-C values by the direct method were slightly but significantly higher (P <0.02) than those by the HPLC method. A quantitative HPLC analysis of the cholesterol concentration in HDL and non-HDL fractions in the supernatant of serum separated by precipitation reagents with different MgCl2 concentrations ranging from 7.3 to 44 mmol/L revealed that reagents with >22 mmol/L MgCl2 precipitated part of HDL as well as non-HDL lipoproteins. The HPLC method providing quantitative and qualitative information with high precision was regarded as being a reliable approach for HDL-C assay. The HPLC can be also used to evaluate alternative methods for cholesterol assay.
Measurement of low-density lipoprotein particle size by high-performance gel-filtration chromatography
Authors: Scheffer Peter G , Bakker Stephan J L , Heine Robert J , Teerlink Tom
Published: January 2020

We describe a new technique for measuring LDL size by high-performance gel-filtration chromatography (HPGC). LDL was subjected to chromatography, and the column effluent was monitored at 280 nm. The retention time of the LDL peak was used to calculate the LDL diameter. We compared the HPGC method with gradient gel electrophoresis (GGE) on 2–10% nondenaturing polyacrylamide gels. In a group of 60 non-insulin-dependent diabetes mellitus patients, LDL size as measured by HPGC and GGE was highly correlated (r = 0.88, P <0.001). Good reproducibility, high precision, and the possibility of analyzing large series of samples are the main advantages of the automated HPGC method. Within-run and between-run CV for LDL size measured by HPGC were <0.1% and 0.2%, respectively. There was a significant inverse association between LDL size measured by HPGC and the logarithm of plasma triglycerides (r = −0.84, P <0.001), and a significant positive association with the LDL free cholesterol/protein ratio (r = 0.89, P <0.001).
Approach to maintaining comparability of biochemical data during long-term clinical trials
Authors: Cull Carole A , Manley Susan E , Stratton Irene M , Neil H Andrew W , Ross Iain S , Holman Rury R , Turner Robert C , Matthews David R
Published: January 2020

Our objective was to design a structured approach to maintaining comparability of biochemical data during a long clinical trial. Maintaining the comparability of clinical and biochemical data obtained in long-term studies is essential, even though analytical methods in the laboratory may be changed, conventions on specimen handling and storage revised, calibration procedures updated, quality-control systems replaced, and secular changes may occur. The United Kingdom Prospective Diabetes Study (UKPDS), a large randomized control trial investigating therapy for type 2 diabetes, was the setting for the study. Data were collected from 5102 subjects randomized since 1977. Our techniques included quality control, external quality assurance, direct comparison of laboratory methods when updating assays and statistical techniques for the detection of unsuspected changes in assay bias, laboratory comparisons of new with old assay methodologies, the realigning of data to current methods, the use of a suitable reference population for long-term monitoring, and rules to aid decision-making about clinical vs statistical significance. Procedures by which comparability of data is assured should be specified for all long-term trials and, where possible, comparison with reference methods should be detailed to allow results from different laboratories to be compared.
Significance of various parameters derived from biological variability of lipoprotein(a), homocysteine, cysteine, and total antioxidant status
Authors: Cobbaert Christa , Arentsen Johannes C , Mulder Paul , Hoogerbrugge Nicoline , Lindemans Jan
Published: January 2020

Analytical and biological components of variability and various derived indices have been determined for lipoprotein(a) [Lp(a)], homocysteine (Hcy), cysteine (Cys), and total antioxidant status (TAOS) in ostensibly healthy adult Caucasians and in stable outpatients with an increased serum Lp(a). In healthy Caucasians, average intraindividual biological CVs (CVb) were 20.0% for Lp(a), 9.4% for Hcy, 5.9% for Cys, and 2.8% for TAOS, CVbs being similar in men and women. In the outpatient group, CVbs were comparable for Hcy, Cys, and TAOS, but significantly lower for Lp(a) (7.5% vs 20.0%; P <0.0001). Moreover, a significant inverse relation between both biological and analytical CVs (CVa) and serum Lp(a) concentrations was demonstrated. We conclude that average CVa and CVb values, and hence average derived indices, are adequate for Hcy, Cys, and TAOS, whereas individual values should be used for Lp(a).
Immunological measurement of transforming growth factor-beta 1 (TGF-β1) in blood; assay development and comparison
Authors: Kropf Jürgen , Schurek Josef O , Wollner Antje , Gressner Axel M
Published: January 2020

Development of a new, sensitive immunoassay for measuring transforming growth factor beta 1 (TGF-β1) is described and compared with four commercially available TGF-β1 immunoassays. Preanalytical conditions were evaluated. The nonlinearity found in serum or plasma is due to masking of TGF-β1 by binding proteins in blood. Mixing TGF-β1 with latency-associated peptide or α2-macroglobulin at physiological concentrations suppressed most of the TGF-β1 signal. Plasma fibronectin showed no effect, even at concentrations exceeding its physiological range. Equilibrium concentrations computed from a model system confirmed the experimental results. Dilutional nonlinearity could be markedly reduced by an appropriately designed activation procedure that minimized the effects of reassociation between TGF-β1 and its binding partners during restoration of a neutral pH. Plasma should be used for measuring TGF-β1 in blood. Because serum TGF-β1 is highly significantly correlated with the platelet count, probably most of the TGF-β1 is released by platelet degranulation.
Improved purification of human bone sialoprotein and development of a homologous radioimmunoassay
Authors: Karmatschek Markus , Maier Ina , Seibel Markus J , Woitge Henning W , Ziegler Reinhard , Armbruster Franz P
Published: January 2020

Bone sialoprotein (BSP) is a phosphorylated skeletal glycoprotein. Here we describe a new procedure for the purification of BSP involving wide-pore reversed-phase HPLC, and the development of a homologous RIA for human BSP. The immunoassay showed linearity between 3 and 120 μg/L, a lower detection limit of 0.7 μg/L, and a mean recovery rate of 99.4%. Intraassay variation was 7.0% (mean = 10.9 μg/L) and 6.1% (mean = 38.8 μg/L), and interassay variation was 9.2% (mean = 11.1 μg/L) and 9.4% (mean = 39.0 μg/L). No cross-reactivity was detected with osteocalcin, osteonectin, or bone alkaline phosphatase. Preliminary clinical evaluation in healthy controls (n = 90) showed a mean serum BSP concentration of 12.1 ± 5.0 μg/L (±SD). BSP was significantly increased in patients with Paget disease of bone, primary and secondary hyperparathyroidism, and also in subjects with renal failure without skeletal involvement. Impairment of hepatic function did not affect serum BSP concentrations.
Intramuscular administration of 5α-dihydrotestosterone heptanoate: changes in urinary hormone profile
Authors: Coutts Sarah B , Kicman Andrew T , Hurst Derek T , Cowan David A
Published: January 2020

A recommended confirmatory procedure for detecting 5α-dihydrotestosterone (DHT) doping in male athletes proposed the use of the urinary concentration ratio of DHT to epitestosterone (EpiT) as the primary marker and those of 5α-androstane-3α,17β-diol (5α-Adiol) to EpiT, luteinizing hormone (LH), and 5β-androstane-3α,17β-diol (5β-Adiol) as secondary markers. Here we investigate the effects on these markers of intramuscular administration of DHT heptanoate (250 mg) to six healthy men. Within 24 h of administration all four markers greatly exceeded the published discrimination limits, remaining above these limits for 10–14 days. All ratios returned to basal values by day 28. In contrast to results after percutaneous administration, 5β-Adiol excretion decreased, probably as a consequence of greater suppression of testicular steroidogenesis. Results were largely in agreement with those obtained after percutaneous administration, although probably augmented by the larger dose and the different route of delivery.
Comparison of NCEP performance specifications for triglycerides, HDL-, and LDL-cholesterol with operating specifications based on NCEP clinical and analytical goals
Authors: Fallest-Strobl Patricia C , Olafsdottir Elin , Wiebe Donald A , Westgard James O
Published: January 2020

The National Cholesterol Education Program (NCEP) performance specifications for methods that measure triglycerides, HDL-cholesterol, and LDL-cholesterol have been evaluated by deriving operating specifications from the NCEP analytical total error requirements and the clinical requirements for interpretation of the tests. We determined the maximum imprecision and inaccuracy that would be allowable to control routine methods with commonly used single and multirule quality-control procedures having 2 and 4 control measurements per run, and then compared these estimates with the NCEP guidelines. The NCEP imprecision specifications meet the operating imprecision necessary to assure meeting the NCEP clinical quality requirements for triglycerides and HDL-cholesterol but not for LDL-cholesterol. More importantly, the NCEP imprecision specifications are not adequate to assure meeting the NCEP analytical total error requirements for any of these three tests. Our findings indicate that the NCEP recommendations fail to adequately consider the quality-control requirements necessary to detect medically important systematic errors.