bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of Pioglitazone on Mitochondria Isolated from Brain and Heart: An Analysis for Probable Drug-Induced Neurotoxicity and Cardiotoxicity
Authors: Seydi Enaytollah , Servati Tina , Samiei Fatemeh , Naserzadeh Parvaneh , Pourahmad Jalal
Published: January 2020

Pioglitazone (PG) is one of the thiazolidinedione (TZDs) drugs used in diabetic patients. TZDs are known as peroxisome proliferator-activated receptor gamma (PPARγ) agonists. Mitochondria are considered as one of the targets of these drugs. The mechanisms of the effect of PG on mitochondria are not well understood. In this study, we investigated the effect of PG on mitochondria isolated from brain and heart. Mitochondrial parameters such as succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) generation, collapse in mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release were evaluated. The results showed that PG at concentrations of 12.5, 25 and 50 µg/ml increased the generation of ROS, the collapse of MMP, mitochondrial swelling and the release of cytochrome c in mitochondria isolated from both brain and heart tissues. The underlying mechanisms of PG induced neuro-toxicity and cardio-toxicity may be associated with changes in mitochondrial function, ROS generation (oxidative stress), and changes in the mitochondrial membrane.
Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?
Authors: Bammer Gabriele , O’Rourke Michael , O’Connell Deborah , Neuhauser Linda , Midgley Gerald , Klein Julie Thompson , Grigg Nicola J. , Gadlin Howard , Elsum Ian R. , Bursztyn Marcel , Fulton Elizabeth A. , Pohl Christian , Smithson Michael , Vilsmaier Ulli , Bergmann Matthias , Jaeger Jill , Merkx Femke , Vienni Baptista Bianca , Burgman Mark A. , Walker Daniel H. , Young John , Bradbury Hilary , Crawford Lynn , Haryanto Budi , Pachanee Cha-aim , Polk Merritt , Richardson George P.
Published: January 2020

Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained.
Simulations of divertor heat flux width using transport code with cross-field drifts under the BOUT++ framework
Authors: Li N. M. , Xu X. Q. , Hughes J. W. , Terry J. L. , Sun J. Z. , Wang D. Z.
Published: January 2020

The fluid transport code [trans-electric field (Er) module] under the BOUT++ framework has been used to simulate divertor heat flux width and boundary Er with all drifts and the sheath potential in the scrape-off layer. The calculated steady state radial Er in the pedestal region has been compared with that of experimental measurements from the Alcator C-Mod tokamak. The magnitude and shape of Er are similar to those of the experimental data. In order to understand the relative role of cross-field drifts vs turbulent transport in setting the heat flux width, four C-Mod enhanced Dα H-mode discharges with a lower single null divertor configuration should be simulated. BOUT++ transport simulations with cross-field drifts included yield similar heat flux width λq to that of experimental measurements (within a factor of 2) from both the probe and the surface thermocouple diagnostics and show a similar trend with plasma current to that of the Eich experimental scaling. The simulations show that both drifts and turbulent transport compete to determine the heat flux width. The magnetic drifts play a dominant role in setting the divertor heat-flux width, while the E × B drift decreases the heat flux width by 10%–25%, leading to improved agreement with the experiment relative to Goldston’s model. A turbulence diffusivity scan (χ⊥) identifies two distinct regimes: a drift dominant regime when χ⊥ is small and a turbulence dominant regime when χ⊥ is large. The Goldston heuristic drift model yields a lower limit of the width λq.
Magnetic exchange induced Weyl state in a semimetal EuCd2Sb2
Authors: Su Hao , Gong Benchao , Shi Wujun , Yang Haifeng , Wang Hongyuan , Xia Wei , Yu Zhenhai , Guo Peng-Jie , Wang Jinhua , Ding Linchao , Xu Liangcai , Li Xiaokang , Wang Xia , Zou Zhiqiang , Yu Na , Zhu Zengwei , Chen Yulin , Liu Zhongkai , Liu Kai , Li Gang , Guo Yanfeng
Published: January 2020

Magnetic Weyl semimetals (WSMs) bearing long-time seeking are still very rare. We have identified herein that EuCd2Sb2, a semimetal belonging to the type IV magnetic space group, hosts a magnetic exchange induced Weyl state via performing high magnetic field magnetotransport measurements and ab initio calculations. In the A-type antiferromagnetic structure, the external field larger than 3.2 T can align all Eu spins to be fully polarized along the c-axis and consequently drive EuCd2Sb2 into a spin polarized state. Magnetotransport measurements up to ∼55–60 T showed striking Shubnikov-de Hass oscillations associated with a nontrivial Berry phase. The ab initio calculations unveiled a phase transition of EuCd2Sb2 from a small gap antiferromagnetic topological insulator to a spin polarized WSM in which the Weyl points emerge along the Γ-Z path. Fermi arcs on (100) and (010) surfaces are also predicted. Meanwhile, the observed large anomalous Hall effect indicates the existence of Weyl points around the Fermi level. The results pave a way toward the realization of various topological states in a single material through the magnetic exchange manipulation.
Fully transparent field-effect transistor with high drain current and on-off ratio
Authors: Park Jisung , Paik Hanjong , Nomoto Kazuki , Lee Kiyoung , Park Bo-Eun , Grisafe Benjamin , Wang Li-Chen , Salahuddin Sayeef , Datta Suman , Kim Yongsung , Jena Debdeep , Xing Huili Grace , Schlom Darrell G.
Published: January 2020

We report a fully transparent thin-film transistor utilizing a La-doped BaSnO3 channel layer that provides a drain current of 0.468 mA/μm and an on-off ratio of 1.5 × 108. The La-doped BaSnO3 channel is grown on a 100–150 nm thick unintentionally doped BaSnO3 buffer layer on a (001) MgO substrate by molecular-beam epitaxy. Unpatterned channel layers show mobilities of 127–184 cm2 V−1 s−1 at carrier concentrations in the low to mid 1019 cm−3 range. The BaSnO3 is patterned by reactive ion etching under conditions preserving the high mobility and conductivity. Using this patterning method, a sub-micron-scale thin film transistor exhibiting complete depletion at room temperature is achieved.
Chemical interface damping for propagating surface plasmon polaritons in gold nanostripes
Authors: Brown Brendan S. , Hartland Gregory V.
Published: January 2020

Leakage radiation microscopy has been used to examine chemical interface damping (CID) for the propagating surface plasmon polariton (PSPP) modes of Au nanostripes—nanofabricated structures with heights of 40 or 50 nm, widths between 2 and 4 µm, and 100 µm lengths. Real space imaging was used to determine the propagation lengths LSPP of the leaky PSPP modes, and back focal plane measurements generated ω vs k dispersion curves, which yield the PSPP group velocities vg. The combination of these two experiments was used to calculate the PSPP lifetime via T1 = LSPP/vg. The difference in T1 times between bare and thiol coated nanostripes was used to determine the dephasing rate due to CID ΓCID for the adsorbed thiol molecules. A variety of different thiol molecules were examined, as well as nanostripes with different dimensions. The values of ΓCID are similar for the different systems and are an order-of-magnitude smaller than the typical values observed for the localized surface plasmon resonances (LSPRs) of Au nanoparticles. Scaling the measured ΓCID values by the effective path length for electron-surface scattering shows that the CID effect for the PSPP modes of the nanostripes is similar to that for the LSPR modes of nanoparticles. This is somewhat surprising given that PSPPs and LSPRs have different properties: PSPPs have a well-defined momentum, whereas LSPRs do not. The magnitude of ΓCID for the nanostripes could be increased by reducing their dimensions, principally the height of the nanostructures. However, decreasing dimensions for the leaky PSPP mode increases radiation damping, which would make it challenging to accurately measure ΓCID.
Tadpoles of the sandpaper frog, Lechriodus fletcheri, hunt mosquito larvae in ephemeral pools
Authors: Gould John
Published: January 2020

Amphibian tadpoles are generally considered to be herbivores or plant-based detritivores that occupy lower trophic levels within freshwater aquatic communities. However, tadpoles are known to incorporate a variety of animal products within their diets as well. There are also many examples of tadpole species occupying higher trophic levels as opportunistic predators of conspecifics and other animals. In this paper, I describe the opportunistic predation of mosquito larvae by tadpoles of the sandpaper frog, Lechriodus fletcheri. Field observations revealed that L. fletcheri tadpoles actively preyed on mosquito larvae at the surface of the water column, using a series of swimming-to-gliding motions to hunt. This swimming routine may be effective for catching mosquito larvae, which respond to water vibrations to evade predation, allowing tadpoles to effectively become ‘invisible’ to the larvae during periods when tail motions are ceased. Given that L. fletcheri tadpoles have a non-specialised omnivorous diet, these findings indicate that the tadpoles of some species have the ability to take up multiple ecological roles within freshwater systems, including as opportunistic predators.
The impact of Brexit on francophone Africa
Authors: Kohnert Dirk
Published: January 2020

The Brexit election in the United Kingdom on 12 December 2019 which brought Boris Johnson to power made it clear beyond doubt that Brexit will come soon. With or without an EU deal, the impact on Africa will be considerable too. Brexit affects not only Commonwealth but also francophone Africa. The range of the impact stretches from having a direct economic bearing on commodity prices and national budgets, to indirect political effects on progressive social networks that contest the post-colonial CFA currency and the murky network of Françafrique. The following briefing provides an overview of the hitherto under-researched questions on the impact of Brexit on African countries outside the Commonwealth of Nations.
Application of an improved version of McDiarmid inequality in finite-key-length decoy-state quantum key distribution
Authors: Chau H F , Ng K C Joseph
Published: January 2020

In practical decoy-state quantum key distribution, the raw key length is finite. Thus, deviation of the estimated single photon yield and single photon error rate from their respective true values due to finite sample size can seriously lower the provably secure key rate R. Current method to obtain a lower bound of R follows an indirect path by first bounding the yields and error rates both conditioned on the type of decoy used. These bounds are then used to deduce the single photon yield and error rate, which in turn are used to calculate a lower bound of the key rate R. Here we report an improved version of McDiarmid inequality in statistics and show how use it to directly compute a lower bound of R via the so-called centering sequence. A novelty in this work is the optimization of the bound through the freedom of choosing possible centering sequences. The provably secure key rate of realistic 100 km long quantum channel obtained by our method is at least twice that of the state-of-the-art procedure when the raw key length ℓ
raw is ≈105–106. In fact, our method can improve the key rate significantly over a wide range of raw key length from about 105 to 1011. More importantly, it is achieved by pure theoretical analysis without altering the experimental setup or the post-processing method. In a boarder context, this work introduces powerful concentration inequality techniques in statistics to tackle physics problem beyond straightforward statistical data analysis especially when the data are correlated so that tools like the central limit theorem are not applicable.
Strain tunable quantum dot based non-classical photon sources
Authors: Yang Jingzhong , Zopf Michael , Ding Fei
Published: January 2020

Semiconductor quantum dots are leading candidates for the on-demand generation of single photons and entangled photon pairs. High photon quality and indistinguishability of photons from different sources are critical for quantum information applications. The inability to grow perfectly identical quantum dots with ideal optical properties necessitates the application of post-growth tuning techniques via e.g. temperature, electric, magnetic or strain fields. In this review, we summarize the state-of-the-art and highlight the advantages of strain tunable non-classical photon sources based on epitaxial quantum dots. Using piezoelectric crystals like PMN-PT, the wavelength of single photons and entangled photon pairs emitted by InGaAs/GaAs quantum dots can be tuned reversibly. Combining with quantum light-emitting diodes simultaneously allows for electrical triggering and the tuning of wavelength or exciton fine structure. Emission from light hole exciton can be tuned, and quantum dot containing nanostructure such as nanowires have been piezo-integrated. To ensure the indistinguishability of photons from distant emitters, the wavelength drift caused by piezo creep can be compensated by frequency feedback, which is verified by two-photon interference with photons from two stabilized sources. Therefore, strain tuning proves to be a flexible and reliable tool for the development of scalable quantum dots-based non-classical photon sources.
Effects of Dy diffusion time on magnetic properties of Nd–Fe–B sintered magnets
Authors: Song Xiao-Ming , Zhang Ting-An , Dou Zhi-He , Pei Wen-Li , Zhou Lian
Published: January 2020

In recent years, significant research efforts were undertaken to enhance coercivity (H

cj
) of Nd-Fe-B sintered magnets. One of the methods is Dy diffusion, which is very effective in improving H

cj
while maintaining the same level of remanence (B

r
). Experiments reported in this work revealed that Dy diffusion differently affected H

cj
of Nd-Fe-B sintered magnets at three diffusion stages: (1) from 0 to 4 h of Dy diffusion, H

cj
increased rapidly from 32.3 to 36.5 kOe as Dy content increased rapidly from 0 to 0.27 wt%; (2) from 4 to 24 h, when Dy content changed from 0.27 to 0.56wt%, H

cj
increased from 36.5 to 38.7 kOe; (3) from 24 to 30 h, H

cj
and Dy content barely changed. Thus, extending Dy diffusion time beyond 24 h period would not yield any improvements. From 0 to 30 h, B

r
slightly decreased from 12.40 to 12.22 kGs. During Dy diffusion, intergranular grain boundaries became continuous and homogeneous, and some micro-defects were repaired. As a result, from 0 to 24 h, H

cj
enhanced significantly while B

r
barely changed. Thus, the Nd-Fe-B sintered magnets with high properties (B

r
= 12.22 kGs, H

cj
 = 38.9 kOe and (BH)max = 36.87 MGOe) were obtained.
Evaluation of microstructural and corrosion resistance of as-cast Cu45Mn25Al15Fe5Cr5Ni5 high entropy alloy
Authors: Abdelghafar K A , Ibrahim M M , Shoeib Madiha A , Waly M A
Published: January 2020

Cu45Mn25Al15Fe5Cr5Ni5 high entropy alloy was prepared using casting route. Detailed microstructural analysis revealed the formation of dendritic structure in the as-cast sample. The results showed that the dendrite (DR) regions are riched with Cu and Mn, while the inter-dendrite (ID) regions are riched with Cr and Fe. Metallographic investigation was conducted using optical microscope and scanning electron microscope as well. Determination of phase analysis was carried out using x-ray diffraction. Corrosion properties were studied via Auto LAB PGSTAT 302N, supplied with Nova software. The investigated alloy demonstrates superior corrosion resistance with average corrosion rate 0.056 mm year−1.
Effects of compaction and heat treatment on the soft magnetic properties of iron-based soft magnetic composites
Authors: Pan Yifan , Peng Jingguang , Qian Liwei , Xiang Zhen , Lu Wei
Published: January 2020

Iron-based soft magnetic composites (SMCs) are promising substitutes for laminate steels in electromagnetic applications due to their excellent magnetic properties and productivity. However, the preparation process is a key factor in deciding the magnetic performance of SMCs. In this work, the Fe-based soft magnetic composites with improved soft magnetic properties were achieved by optimizing the compaction and the annealing process. Results showed that the core–shell structure of powders which would directly have an impact on the permeability and the core loss of the SMCs could be affected by the compaction and the annealing process. In addition, the magnetic properties were enhanced by tuning the microstructure. As a result, the optimal magnetic performance of the compact with high permeability and low total core loss was obtained. The real part of the permeability of the soft magnetic composites could reach a maximal value of 336.8 and a rather low core loss of 2.5 W Kg−1 (measured at 50 mT and 5 kHz). Therefore, soft magnetic composites with enhanced magnetic properties were obtained by optimizing the powder metallurgy (PM) process in this study.
Elastic properties of single crystal Bi12SiO20 as a function of pressure and temperature and acoustic attenuation effects in Bi12MO20 (M = Si, Ge and Ti)
Authors: Haussühl Eiken , Reichmann Hans Josef , Schreuer Jürgen , Friedrich Alexandra , Hirschle Christian , Bayarjargal Lkhamsuren , Winkler Björn , Alencar Igor , Wiehl Leonore , Ganschow Steffen
Published: January 2020

A comprehensive study of sillenite Bi12SiO20 single-crystal properties, including elastic stiffness and piezoelectric coefficients, dielectric permittivity, thermal expansion and molar heat capacity, is presented. Brillouin-interferometry measurements (up to 27 GPa), which were performed at high pressures for the first time, and ab initio calculations based on density functional theory (up to 50 GPa) show the stability of the sillenite structure in the investigated pressure range, in agreement with previous studies. Elastic stiffness coefficients c
11 and c
12 are found to increase continuously with pressure while c
44 increases slightly for lower pressures and remains nearly constant above 15 GPa. Heat-capacity measurements were performed with a quasi-adiabatic calorimeter employing the relaxation method between 2 K and 395 K. No phase transition could be observed in this temperature interval. Standard molar entropy, enthalpy change and Debye temperature are extracted from the data. The results are found to be roughly half of the previous values reported in the literature. The discrepancy is attributed to the overestimation of the Debye temperature which was extracted from high-temperature data. Additionally, Debye temperatures obtained from mean sound velocities derived by Voigt-Reuss averaging are in agreement with our heat-capacity results. Finally, a complete set of electromechanical coefficients was deduced from the application of resonant ultrasound spectroscopy between 103 K and 733 K. No discontinuities in the temperature dependence of the coefficients are observed. High-temperature (up to 1100 K) resonant ultrasound spectra recorded for Bi12
MO20 crystals revealed strong and reversible acoustic dissipation effects at 870 K, 960 K and 550 K for M = Si, Ge and Ti, respectively. Resonances with small contributions from the elastic shear stiffness c
44 and the piezoelectric stress coefficient e
123 are almost unaffected by this dissipation.
About the surface area to volume relations of open cell foams
Authors: August A , Nestler B
Published: January 2020

Many useful applications of solid open-cell foams make use of their enormous surface, compared to their volume. The large surface is accompanied by a large interface between foam and filling of a fluid, gas or another solid forming a composite material. Due to the large interface, heat exchange between the involved materials takes place in a particularly efficient manner making open cell metallic foams to base materials for heat exchange and heat systems of increasing importance. But what is the mathematical connection between the solid bulk volume fraction and the surface of these porous materials? This question is investigated through the evaluation of 5000 synthetic, randomly generated open-cell cellular structures of different material ratios.
Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex
Authors: Gram Inger T , Park Song-Yi , Wilkens Lynne R , Haiman Christopher A , Le Marchand Loïc
Published: January 2020

The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.
Flexibly Accounting for Exposure Misclassification With External Validation Data
Authors: Edwards Jessie K , Cole Stephen R , Fox Matthew P
Published: January 2020

Measurement error is common in epidemiology, but few studies use quantitative methods to account for bias due to mismeasurement. One potential barrier is that some intuitive approaches that readily combine with methods to account for other sources of bias, like multiple imputation for measurement error (MIME), rely on internal validation data, which are rarely available. Here, we present a reparameterized imputation approach for measurement error (RIME) that can be used with internal or external validation data. We illustrate the advantages of RIME over a naive approach that ignores measurement error and MIME using a hypothetical example and a series of simulation experiments. In both the example and simulations, we combine MIME and RIME with inverse probability weighting to account for confounding when estimating hazard ratios and counterfactual risk functions. MIME and RIME performed similarly when rich external validation data were available and the prevalence of exposure did not vary between the main study and the validation data. However, RIME outperformed MIME when validation data included only true and mismeasured versions of the exposure or when exposure prevalence differed between the data sources. RIME allows investigators to leverage external validation data to account for measurement error in a wide range of scenarios.
Development and perception of a multiple-site nontraditional postgraduate year 1 residency program
Authors: Hawkins Smith Carla , Stevens Joanie Spiro , Rosa Morales Leslie , Martinez Leyner , Camejo Madeline , Bryant Keysha
Published: January 2020

Purpose

To describe the development and perception of a multiple-site nontraditional postgraduate year 1 (PGY1) residency program from the resident and preceptor perspectives.

A multiple-site nontraditional residency program was developed within a Florida health system to increase the education level and clinical responsibilities of hospital staff pharmacists. The program provided pharmacists interested in residency training an opportunity to pursue postgraduate credentials while maintaining their current position. The nontraditional residency program was implemented at 1 site and subsequently expanded across multiple affiliated hospital sites due to its success. Pharmacists currently working in the health system’s network of hospitals for at least 2 years were eligible to enter into the 24-month program after successfully completing the application, interview, and matching process. The number of nontraditional resident positions available has varied by residency year and site. Offering this opportunity has increased the clinical knowledge of pharmacists, exposed them to a variety of practice areas, and increased their departmental contributions. In response to a request for feedback regarding the multiple-site nontraditional program, both residents and preceptors have reported benefits and challenges.

Conclusion

Adequate resources are needed and a number of factors must be considered in developing a multiple-site nontraditional PGY1 residency program. Although there are potential challenges, it is perceived that the benefits justify continuation of the program.
Bias due to Berkson error: issues when using predicted values in place of observed covariates
Authors: Haber Gregory , Sampson Joshua , Graubard Barry
Published: January 2020

Studies often want to test for the association between an unmeasured covariate and an outcome. In the absence of a measurement, the study may substitute values generated from a prediction model. Justification for such methods can be found by noting that, with standard assumptions, this is equivalent to fitting a regression model for an outcome variable when at least one covariate is measured with Berkson error. Under this setting, it is known that consistent or nearly consistent inference can be obtained under many linear and nonlinear outcome models. In this article, we focus on the linear regression outcome model and show that this consistency property does not hold when there is unmeasured confounding in the outcome model, in which case the marginal inference based on a covariate measured with Berkson error differs from the same inference based on observed covariates. Since unmeasured confounding is ubiquitous in applications, this severely limits the practical use of such measurements, and, in particular, the substitution of predicted values for observed covariates. These issues are illustrated using data from the National Health and Nutrition Examination Survey to study the joint association of total percent body fat and body mass index with HbA1c. It is shown that using predicted total percent body fat in place of observed percent body fat yields inferences which often differ significantly, in some cases suggesting opposite relationships among covariates.
Generalized additive regression for group testing data
Authors: Liu Yan , McMahan Christopher S , Tebbs Joshua M , Gallagher Colin M , Bilder Christopher R
Published: January 2020

In screening applications involving low-prevalence diseases, pooling specimens (e.g., urine, blood, swabs, etc.) through group testing can be far more cost effective than testing specimens individually. Estimation is a common goal in such applications and typically involves modeling the probability of disease as a function of available covariates. In recent years, several authors have developed regression methods to accommodate the complex structure of group testing data but often under the assumption that covariate effects are linear. Although linearity is a reasonable assumption in some applications, it can lead to model misspecification and biased inference in others. To offer a more flexible framework, we propose a Bayesian generalized additive regression approach to model the individual-level probability of disease with potentially misclassified group testing data. Our approach can be used to analyze data arising from any group testing protocol with the goal of estimating multiple unknown smooth functions of covariates, standard linear effects for other covariates, and assay classification accuracy probabilities. We illustrate the methods in this article using group testing data on chlamydia infection in Iowa.
Civic Crowdfunding for Social Work Research: Opportunities, Challenges and Strategies
Authors: Cheung Johnson Chun-Sing , Rogers Justin Mark
Published: January 2020

Civic crowdfunding for research purposes has been an emerging trend in scientific fields over the past few years. This article presents findings from a mixed methods analysis of 152 social science research projects that campaigned for crowdfunding. A total of US$583,074 was raised through the support of 6,663 backers amongst the 150 successfully funded projects. This study offers specific lessons for social work researchers engaging in crowdfunding campaigns. The data show that projects supported by endorsers and initiated by faculties were able to solicit more backers and funds. Another key finding is that the campaigns that had videos for promotional purposes were the most successful, but video length does not affect backers’ consideration. The article presents the potential ethical challenges for social work researchers in this crowdfunding arena. In what may first appear to be a democratic and emancipatory space, decisions are actually made about what topics are worthy of financing by people who have access to the online platforms and the disposable income to back the project. Nevertheless, these platforms offer a route to research funding for academics, practitioners and service user groups in a context where funding from research councils and foundations is increasingly limited and competitive.
A new look at the role of urinalysis in the history of diagnostic medicine
Authors: White William I
Published: January 2020

Before this century, urine was the predominant body fluid used by the physician for diagnosis and prognosis. Uroscopy, or urinalysis by the senses, has usually been treated disparagingly in historical accounts of diagnostic medicine. Although uroscopy was at times used fraudulently, the thoughtful use of urinalysis was probably an important part of diagnosis for the physician, even before the chemical analysis of urine.
Capillary electrophoresis--a new clinical tool
Authors: Chen Fu-TalA , Liu Cheng-Ming , Hsieh You-Zun , Sternberg James C
Published: January 2020

The potential clinical diagnostic utility of capillary electrophoresis in an open-tubular column is established. Separation patterns for serum proteins by conventional agarose gel electrophoresis can be faithfully reproduced by a capillary electrophoresis procedure that provides the complete run data in 8 min. Hemoglobin variants can be separated within 10 min. The capillary electrophoresis separations are performed reliably and reproducibly in an untreated 75 micron (i.d.) x 25 cm fused-silica column. Diluted serum or hemoglobin samples can be loaded on an automated instrument with on-line injection, detection, and quantification, providing a truly "walkaway" electrophoresis system.
Microparticle-enhanced nephelometric immunoassay (Nephelia) for immunoglobulins G, A, and M
Authors: Cuilliere M L , Montagne P , Bessou Th , el Omari R , Riochet D , Varcin P , Laroche P , Prud'homme Ph , Marchand J , Flecheux O , Pau B , Duheille J
Published: January 2020

Covalent binding of gamma chains of IgG, whole IgA, and mu chains of IgM on polyfunctional hydrophilic microspheres (MS) yields MS-Ig conjugates, usable as reagents in new microparticle-enhanced nephelometric immunoassays (Nephelia). The principle of the assays is inhibition by free analyte (IgG, IgA, and IgM) of agglutination of the MS-Ig conjugate with specific antiserum, the light scattered by the aggregates being measured with a nephelometer. The immunoglobulin assays developed are easy to perform (single-step assays, no washing or phase separation) and sensitive (high dilution of biological samples to exclude interferences and pretreatment). Analytical recovery results (95.4-101.2%) and correlations with generally used commercial assays (r = 0.86-0.98) indicate that the assays are accurate for large concentration ranges of immunoglobulins. Precision sxtudy gives CVs = 2.8-9.6%. Nephelia appears to be useful for quantifying a large variety of biological molecules.
Carbonic anhydrase III in serum in muscular dystrophy and other neurological disorders: relationship with creatine kinase
Authors: Ohta Mitsuhlro , Itagaki Yasuko , Itoh Nobuyukl , Hayashi Kyozo , Nishitani Hirosh , Ohta Klyoe
Published: January 2020

We measured with a radioimmunoassay the concentrations of carbonic anhydrase III (CA-III, EC 4.2.1.1) in sera from 68 patients with muscular dystrophy, 10 carriers of Duchenne muscular dystrophy (DMD), and 63 patients with other neurological disorders. The values obtained were compared with those for creatine kinase (CK, EC 2.7.3.2). Serum CA-III was strikingly increased in patients with DMD (mean, 274.4 micrograms/L) and congenital (Fukuyama-type) (182.8 micrograms/L) and limb-girdle (203.7 micrograms/L) dystrophies and positively correlated with the activities of CK in patients with DMD. CA-III concentration decreased with the subjects' age and the severity of the disease, similar to the tendency observed between age or severity and the concentration of CK. We found moderately increased CA-III in patients with polymyositis, myotonic dystrophy, amyotrophic lateral sclerosis, spinal progressive muscular atrophy, or Kugelberg-Welander disease and in carriers of DMD.
Human anti-murine antibody interference in measurement of carcinoembryonic antigen assessed with a double-antibody enzyme immunoassay
Authors: Price Theresa , Beatty Barbara G , Beatty J David , McNally Alan J
Published: January 2020

Fifty-eight plasma specimens from 30 patients who had undergone presurgical radioimmunoscintigraphy with 111In-labeled anti-carcinoembryonic antigen (CEA) murine monoclonal antibody (Mab) and who had no clinical evidence of disease after surgical resection showed increased concentrations of CEA (greater than or equal to 5 micrograms/L) in plasma when studied with the previously available commercial CEA enzyme immunoassay (EIA) from Roche. The possible role of anti-murine antibody (HAMA) interference was addressed by adding mouse IgG (mIgG) to the plasma (2 g/L) before assay. Fifteen specimens (26%) showed no change in CEA (reflecting a true increase as shown by the original results), 22 (38%) showed a decrease in CEA of greater than 15% but remained positive (reflecting an artefactual increase), and 21 (36%) became CEA-negative (less than or equal to 5 micrograms/L; reflecting a false increase). Subsequently, we assayed the same samples with a modified version of this CEA EIA kit and 47 specimens remained CEA positive (greater than 5 micrograms/L): 25 (53%) were truly increased, 12 (26%) remained artefactually increased, and 10 (21%) continued to show a false increase. The degree of interference in the original EIA kit correlated with the plasma concentration of HAMA (P less than 0.005). All artefactually and falsely increased CEA values observed in both kits were corrected by addition of polyclonal mIgG or of a mixture of IgG1, IgG2a, and IgG2b Mabs before assay. This correction is important in the follow-up of patients who receive murine Mabs for treatment or diagnosis.
Diagnostic and genetic studies in 43 patients with classic cystinuria
Authors: Byrd DennIs J , Lind Marion , Brodehl Johannes
Published: January 2020

We present results for laboratory screening and diagnostic tests--cyanide-nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine-lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria.
International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B
Authors: Marcovina S M , Albers J J , Dati F , Ledue T B , Ritchie R F
Published: January 2020

To minimize differences in apolipoprotein measurements among laboratories and methods, a standardization program involving common suitable reference material is needed. The Committee on Apolipoproteins of the International Federation of Clinical Chemistry initiated a collaborative study for the standardization of test systems for measuring apolipoproteins (apo) A-I and B, with 25 company laboratories and three research laboratories involved in apolipoprotein analysis to: (a) evaluate calibration differences among the test systems; (b) evaluate whether comparability of the data can be achieved with the use of frozen serum pools to recalibrate the different systems; and (c) evaluate and select suitable candidate reference material. We used 26 test systems for apo A-I and 28 for apo B. Relatively modest differences were found in calibration for apo A-I, but very wide differences were observed for apo B methods. After uniform calibration, the overall among-laboratory CV for apo B decreased from 19% to 6%. Three lyophilized serum preparations for apo A-I and three liquid-stabilized serum preparations for apo B were selected for further evaluation as candidate international reference materials.
Association between urinary N-acetyl-beta-glucosaminidase and its isoenzyme patterns and microangiopathy in type 1 diabetes mellitus
Authors: Agardh C D , Agardh E , Isaksson A , Hultberg B
Published: January 2020

Urinary N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes (NAG A and NAG B) in samples from 87 type 1 diabetic patients and 40 apparently healthy reference subjects were studied with enzyme immunoassays. The diabetic patients had higher concentrations of urinary NAG than did the control subjects (P less than 0.01), but the isoenzyme pattern did not differ. There was a positive correlation between metabolic control (Hb A1c concentrations) and total NAG (P less than 0.01), NAG A (P less than 0.01), and NAG B (P less than 0.001). The diabetic patients were divided into three groups, depending on the degree of retinopathy. Subjects with severe forms of retinopathy did not have increased concentrations of urinary NAG unless they had concomitant nephropathy. The isoenzyme pattern was similar irrespective of degree of retinopathy or nephropathy. The results indicate that concentrations of urinary NAG are positively correlated to the degree of nephropathy, whereas there is no such correlation to the degree of retinopathy.
Studies on the measurement of protein S in plasma
Authors: Bovill E G , Landesman M M , Busch S A , Fregeau G R , Mann K G , Tracy R P
Published: January 2020

The anticoagulant factor Protein S circulates in two major forms, free and bound to C4b binding protein (C4BP). We report a monoclonal antibody-based enzyme-linked immunosorbent assay of human Protein S that is sensitive (detection limit 30 ng) and free of notable competition from other vitamin K-dependent proteins. We demonstrate assay sensitivity to Protein S-C4BP complex, as well as to free Protein S by (a) results of immunoaffinity chromatography involving the assay antibody; (b) parallelism between the standard curve and a plasma dilution curve, including dilutions greater than 100-fold; (c) lack of effect of added C4BP on Protein S values; and (d) reactivity in the assay by high-molecular-mass plasma Protein S in gel permeation studies. These latter studies also indicate that uncomplexed Protein S has an apparent molecular mass of approximately 150,000 Da, attributable to either polymerization or conformational considerations. Inter- and intra-assay CVs were 9.8% and 5.1%, respectively, and 90% of Protein S added to plasma was recovered. Reference ranges (mean and SD) for total Protein S in middle-aged normal subjects were 16.6 (1.9) mg/L for men (n = 54) and 16.0 (3.0) mg/L for women (n = 38). In the polyethylene glycol precipitation method, the reference values for free Protein S were 5.4 (1.6) mg/L for men and 4.4 (1.1) mg/L for women.
Monoclonal antibody-based discrepancies between two-site immunometric tests for lutropin
Authors: Pettersson K , Ding Y Q , Huhtaniemi I
Published: January 2020

We compared five two-site immunometric assays (including three commercially available kits) for measuring lutropin (LH) in serum. Four of the assays involved monoclonal antibodies directed against the alpha-beta dimer, intact LH; these assays measured significantly lower concentrations of LH in 19 (out of 83) samples than did a commercial method not involving such antibodies. In five serum samples, two of the intact LH assays failed to detect any significant immunoreactivity above the detection limit. Findings of normal in vitro LH bioactivity in these samples did not confirm the low immunoreactivity of the intact LH assays. The inability of these assays to detect bioactive LH creates confusion in daily, routine testing as well as in research monitoring of bio/immuno ratios. The data presented here confirm our previous findings (Clin Chem 1991;37:333-40) and emphasize the need to avoid the use of monoclonal antibodies specific for the intact LH dimer.
Atrial natriuretic peptide assayed after immunoextraction with magnetic iron particles
Authors: Török A , Penke B
Published: January 2020

We investigated a new method for the immunoextraction of atrial natriuretic peptide (ANP) from plasma. Anti-ANP antibody was coupled to magnetizable iron particles by various coupling methods; both carboxyl terminal and amine terminal iron particles were examined. Introducing a chemical spacer between the iron particles and the antibody improved binding with ANP. The most efficient and reliable immunoextraction involves coupling the ANP antibody to amine terminal iron particles with bis-succinimidyl-suberate. Analytical recovery of ANP from this antibody-coupled suspension was 104% (SD 7.8%). We measured extracted samples by RIA. Standards were included in the extraction step. The detection limit of the assay was 3 ng/L. Patients' samples were assayed after both immunoextraction (y) and Sep-Pak C18 extraction (x); ANP values obtained with these methods correlated highly significantly y = 1.02x - 5.57 ng/L [r = 0.9302, n = 19, SE intercept = 5.7 (not significant), SE slope = 0.10 (P less than 0.0001)]. The method presented is potentially a reliable, efficacious immunoextraction method for ANP.
Pentobarbital quantification in the presence of phenobarbital by fluorescence polarization immunoassay
Authors: Earl R , Sobeski L , Timko D , Markin R
Published: January 2020

We developed a method for measuring pentobarbital in samples that also contain phenobarbital. The phenobarbital is destroyed by adding sodium hydroxide and then heating at 95 degrees C for 60 min. Pentobarbital is not affected by this pretreatment and can then be measured with an Abbott TDx barbiturates kit. Using this method, we obtained an average analytical recovery of 98% of added pentobarbital and a correlation of y = 0.953x + 3.4 vs HPLC. The intra-assay CV was 3.7% at 25.8 mg/L; the interassay CV was 6.2% at 16.1 mg/L. Other long-acting barbiturates, e.g., hexobarbital, are also effectively destroyed by this alkali pretreatment. Other short-acting barbiturates, e.g., secobarbital, are not removed and would produce an interference.