bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term outcome of renal transplantation in childhood‐onset anti‐neutrophil cytoplasmic antibody–associated vasculitis
Authors: Nagasawa Takeshi , Miura Kenichiro , Kaneko Naoto , Yabuuchi Tomoo , Ishizuka Kiyonobu , Chikamoto Hiroko , Akioka Yuko , Hisano Masataka , Hattori Motoshi
Published: January 2020

Background

There have been a few reports of RTx for AAV in children; however, post‐transplant recurrence rate and long‐term prognosis remain unclear. Here, we describe the long‐term outcomes of RTx in childhood‐onset AAV.

Methods

We conducted a retrospective study of children who underwent RTx for AAV between 1999 and 2017 and had a follow‐up period of >2 years.

Results

Seven patients consisting of three children with MPA and four with RLV were analyzed. Age at Dx was 5.9 (median; range, 4.1‐14.5) years. PD was instituted in all patients, and median time on dialysis was 26 (range, 14‐63) months. Age at RTx was 12.8 (median; range, 8.7‐16.3) years. There were no recurrences of AAV noted during the median follow‐up period of 7.0 (range, 2.7‐18.8) years after RTx. Graft loss occurred in one patient due to non‐adherence. Estimated glomerular filtration rate of the remaining patients at the last follow‐up was 73.0 (median; range, 50.7‐93.9) mL/min/1.73 m2. No malignancies and deaths occurred during the observational period.

Conclusions

Our study suggests that RTx for AAV with ESRD is a potentially safe and effective treatment choice for children with AAV.
Picking Up and Defending the Faith: Activism and Radicalism Among Muslim Converts in the United States
Authors: Fodeman Ari D. , Snook Daniel W. , Horgan John G.
Published: January 2020

Muslim converts tend to be overrepresented in terrorist activity compared to fellow nonconvert Muslims. However, due to the low base rate of terrorism activity, there is a significant risk that this overrepresentation is a “false positive.” We therefore tested the prevalence of far more common, but potentially antecedent, cognitions to terrorism—activism and radicalism––among convert and nonconvert Muslims. We surveyed 356 American Muslim adults, of which 177 were self‐identified converts, with the Activism and Radicalism Intention Scale or ARIS. We found that converts as compared to nonconverts do demonstrate higher activism and radicalism intention scores. We also found that activism fully mediates the relationship between conversion and radicalism. This suggests that converts may be more likely to engage in radical behavior (such as terrorism) than nonconverts, but only because they are more likely to engage in activism than nonconverts. We discuss these findings in light of current psychology and political mobilization literature, then we offer suggestions for future research on the relationships between conversion, activism, radicalism, and terrorism.
Quantitative ultrasound elastography and biometry of the bitch uterus in the early puerperium after vaginal delivery and caesarean section
Authors: Simões Ana Paula Rodrigues , Maronezi Marjury Cristina , Uscategui Ricardo Andres Ramirez , Avante Michelle Lopes , Gasser Beatriz , Silva Priscila , Pavan Letícia , Maciel Giovanna Serpa , Pelógia Marina Emanoella Seruti , Vicente Wilter Ricardo Russiano , Feliciano Marcus Antonio Rossi
Published: January 2020

Elastography is an actual imaging method used to qualitatively and quantitatively evaluate the elastic properties of tissues. The aim of this study was to evaluate and compare uterine tissue biometry and stiffness during post‐partum period in brachycephalic bitches (n = 12) after c‐section (GCS; n = 8) or normal delivery (GNB; n = 4). These animals were evaluated daily by abdominal ultrasound from the day of delivery until the 10th day post‐partum; measuring uterine diameter, myometrial and endometrial thickness (mm) and shear wave velocity (SWV; m/s), by B‐mode and ARFI (acoustic radiation force impulse) elastography, respectively. Uterine diameter was higher (p = .012) in animals submitted to c‐section (15.26 ± 4.73 mm) than in normal birth (12.53 ± 2.64 mm) during the first 7 days post‐partum. Uterine thickness gradually involuted in both groups (p < .0001), the myometrium during the first 9 days (p = .005) and the endometrium during the first 6 days (p = .003). The myometrial and endometrial SWVs were similar between types of delivery (p = .7846 and .8273) and presented a gradual increase (p = .411; .0043, respectively), during the first 10 days post‐partum. It was concluded that bitches with normal delivery had smaller uterine thickness and faster puerperal involution than submitted to c‐section, while uterine tissue stiffness was similar between delivery types and increased gradually during post‐partum.
Carbonate slope re‐sedimentation in a tectonically‐active setting (Western Sicily Cretaceous Escarpment, Italy)
Authors: Randazzo Vincenzo , Le Goff Johan , Di Stefano Pietro , Reijmer John , Todaro Simona , Cacciatore Maria Simona
Published: January 2020

Tectonic processes are widely considered as a mechanism causing carbonate platform margin instabilities leading to the emplacement of mass transport deposits and calciturbidites. However, only few examples establishing a clear link between tectonics and re‐sedimentation processes are known from the literature. The two‐dimensional and three‐dimensional wire‐cut walls of hundreds of quarries extracting ornamental limestones (for example, Perlato di Sicilia) from the Western Sicily Cretaceous Escarpment in Italy expose a series of mass transport deposits. The depositional architecture, spatial facies distribution and sedimentary features of these deposits were studied in detail. Thin section analysis was used to define the microfacies characteristics and to determine the age of the re‐sedimented limestones. Eleven facies types grouped into four facies associations were recognized that defined specific depositional processes and environments. The stratigraphic architecture of the slope was reconstructed using four composite facies successions based on the detailed analysis and correlation of the field sections. The palaeoslope orientation was reconstructed based on the analysis of synsedimentary faults, slump scars and pinch‐out geometries. The Western Sicily Cretaceous Escarpment was strongly influenced by synsedimentary transtensional tectonics in combination with magmatic processes, as suggested by the presence of tuffites and pillow lava intercalations within the re‐sedimented carbonate series. These volcanics point to a major role of crustal shear as a trigger for mass transport deposit emplacement. The facies distribution along the Western Sicily Cretaceous Escarpment delivers new insights into the deformation processes accompanying the crustal extension of the Cretaceous western Tethys realm.
ATP binding cassette transporters ABCG1 and ABCG16 affect reproductive development via auxin signalling in Arabidopsis
Authors: Liu Liping , Zhao Lihua , Chen Piaojuan , Cai Hanyang , Hou Zhimin , Jin Xingyue , Aslam Mohammad , Chai Mengnan , Lai Linyi , He Qing , Liu Yanhui , Huang Xiaoyi , Chen Huihuang , Chen Yingzhi , Qin Yuan
Published: January 2020

Angiosperm reproductive development is a complex event that includes floral organ development, male and female gametophyte formation and interaction between the male and female reproductive organs for successful fertilization. Previous studies have revealed the redundant function of ATP binding cassette subfamily G (ABCG) transporters ABCG1 and ABCG16 in pollen development, but whether they are involved in other reproductive processes is unknown. Here we show that ABCG1 and ABCG16 were not only expressed in anthers and stamen filaments but also enriched in pistil tissues, including the stigma, style, transmitting tract and ovule. We further demonstrated that pistil‐expressed ABCG1 and ABCG16 promoted rapid pollen tube growth through their effects on auxin distribution and auxin flow in the pistil. Moreover, disrupted auxin homeostasis in stamen filaments was associated with defective filament elongation. Our work reveals the key functions of ABCG1 and ABCG16 in reproductive development and provides clues for identifying ABCG1 and ABCG16 substrates in Arabidopsis.
Trauma‐induced primary hypoparathyroidism following severe bite wound injury to the neck in a dog
Authors: Wolf Johanna , Vigani Alessio , Schaer Michael
Published: January 2020

Objective

To describe the clinical presentation and outcome of a dog with primary hypoparathyroidism secondary to cervical bite wounds.

Case Summary

A 3‐year‐old male intact Chihuahua presented after being attacked by a large breed dog. The dog sustained severe cervical lacerations, exposing the trachea and jugular veins. A portion of the right thyroid gland was missing. The dog was stabilized before wound debridement and closure. Ionized calcium concentrations were within reference range at the time of presentation. Forty‐eight hours after the initial trauma, the dog was presented in lateral recumbency with signs of hypovolemic shock, muscle tremors, and hyperthermia. Bloodwork showed severe ionized hypocalcemia with low normal parathyroid hormone concentration consistent with acute primary hypoparathyroidism. The dog was managed initially with IV calcium gluconate and calcitriol, then long‐term oral calcium carbonate and vitamin D3. After 6 months, the dog was successfully weaned off calcium supplementation.

New or Unique Information Provided

This is the first described case of traumatic primary hypoparathyroidism after a bite injury to the neck in a dog.
Comparison of Sudoku Solving Skills of Preschool Children Enrolled in the Montessori Approach and the National Education Programs Yıldız Güven1, Cihat Gültekin1, A. Beyzanur Dedeoğlu1
Authors: Guven Yildiz , Gültekin Cihat , Dedeoğlu A. Beyzanur
Published: January 2020

According to Johnson-Laird (2010), sudoku, a mind game, is based on a pure deduction and reasoning processes. This study analyzed sudoku solving skills of preschool children and to ascertain whether there was a difference between children who were educated according to the Ministry of Education preschool education program and the Montessori approach. Sudoku skills of children were analyzed by gender, age, duration of preschool attendance, mother’s and father’s education level and previous experience of playing sudoku using a 12-question Sudoku Skills Measurement Tool developed for this research study.The study sample of the study consisted of 118 children (57 girls, 61 boys) aged between 54-77 months. The findings showed that there was no significant difference in sudoku skills by gender. However, sudoku skills varied with age (54-65 months and 66-77 months) in favor of older groups. Children's sudoku skills were more developed with an increase in education level of either parent. Children who had been in preschool for longer had higher sudoku scores. A previous experience of playing sudoku did not impact sudoku scores. Sudoku skills of children who were educated according to the Montessori program were more developed compared to those of children educated according to Ministry of National Education program.
Optimal control of fractional integro-differential systems based on a spectral method and grey wolf optimizer
Authors: Khanduzi Raheleh , Ebrahimzadeh Asyieh , Panjeh Ali Beik Samaneh
Published: January 2020

This paper elaborated an effective and robust metaheuristic algorithm with acceptable performance based on solution accuracy. The algorithm applied in solution of the optimal control of fractional Volterra integro-differential (FVID) equation which be substituted by nonlinear programming (NLP). Subsequently the FIVD convert the problem to a NLP by using spectral collocation techniques and thereafter we execute the grey wolf optimizer (GWO) to improve the speed and accuracy and find the solutions of the optimal control and state as well as the optimal value of the cost function. It is mentioned that the utilization of the GWO is simple, due to the fact that the GWO is global search algorithm, the method can be applied to find optimal solution of the NLP. The efficiency of the proposed scheme is shown by the results obtained in comparison with the local methods. Further, some illustrative examples introduced with their approximate solutions and the results of the present approach compared with those achieved using other methods.
Analytical and approximate solution of two-dimensional convection-diffusion problems
Authors: Günerhan Hatıra
Published: January 2020

In this work, we have used reduced differential transform method (RDTM) to compute an approximate solution of the Two-Dimensional Convection-Diffusion equations (TDCDE). This method provides the solution quickly in the form of a convergent series. Also, by using RDTM the approximate solution of two-dimensional convection-diffusion equation is obtained. Further, we have computed exact solution of non-homogeneous CDE by using the same method. To the best of my knowledge, the research work carried out in the present paper has not been done, and is new. Examples are provided to support our work.
Effect of differential muscle activation patterns on muscle deoxygenation and microvascular haemoglobin regulation
Authors: Okushima Dai , Poole David C. , Barstow Thomas J. , Kondo Narihiko , Chin Lisa M. K. , Koga Shunsaku
Published: January 2020

New Findings

What is the central question of this study?

Does the presence and extent of heterogeneity in the ratio of O2 delivery to uptake across human muscles relate specifically to different muscle activation patterns?

What is the main finding and its importance?

During ramp incremental knee‐extension and cycling exercise, the profiles of muscle deoxygenation (deoxy[haemoglobin + myoglobin]) and diffusive O2 potential (total[haemoglobin + myoglobin]) in the vastus lateralis corresponded to different muscle activation strategies. However, this was not the case for the rectus femoris, where muscle activation and deoxygenation profiles were dissociated and might therefore be determined by other structural and/or functional attributes (e.g. arteriolar vascular regulation and control of red blood cell flux).

Near‐infrared spectroscopy has revealed considerable heterogeneity in the ratio of O2 delivery to uptake as identified by disparate deoxygenation {deoxy[haemoglobin + myoglobin] (deoxy[Hb + Mb])} values in the exercising quadriceps. However, whether this represents a recruitment phenomenon or contrasting vascular and metabolic control, as seen among fibre types, has not been established. We used knee‐extension (KE) and cycling (CE) incremental exercise protocols to examine whether differential muscle activation profiles could account for the heterogeneity of deoxy[Hb + Mb] and microvascular haemoconcentration (i.e. total[Hb + Mb]). Using time‐resolved near‐infrared spectroscopy for the quadriceps femoris (vastus lateralis and rectus femoris) during exhaustive ramp exercise in eight participants, we tested the following hypotheses: (i) the deoxy[Hb + Mb] (i.e. fractional O2 extraction) would relate to muscle activation levels across exercise protocols; and (ii) KE would induce greater total[Hb + Mb] (i.e. diffusive O2 potential) at task failure (i.e. peak O2 uptake) than CE irrespective of muscle site. At a given level of muscle activation, as assessed by the relative integrated EMG normalized to maximal voluntary contraction (%iEMGmax), the vastus lateralis deoxy[Hb + Mb] profile was not different between exercise protocols. However, at peak O2 uptake and until 20% iEMGmax for CE, rectus femoris exhibited a lower deoxy[Hb + Mb] (83.2 ± 15.5 versus 98.2 ± 19.4 μm) for KE than for CE (P < 0.05). The total[Hb + Mb] at peak O2 uptake was not different between exercise protocols for either muscle site. These data support the hypothesis that the contrasting patterns of convective and diffusive O2 transport correspond to different muscle activation patterns in vastus lateralis but not rectus femoris. Thus, the differential deoxygenation profiles for rectus femoris across exercise protocols might be dependent upon specific facets of muscle architecture and functional haemodynamic events.
All-Solid-State Asymmetric Supercapacitor Based on Ni–Co Layered Double Hydroxide and rGO Nanocomposite Deposited on Ni Foam
Authors: Lokhande P. E. , Chavan U. S.
Published: January 2020

In recent years, supercapacitors have been extensively exploited as an alternative energy storage technology in various fields such as electronics, computer, and mechanical. In this context, we have reported the utilization of the Ni–Co LDH/rGO nanostructure, deposited on the 3D conductive nickel substrate, to fabricate electrode for supercapacitor application. The film formed on the nickel substrate demonstrated superior electric conductivity and higher surface area which resulted in rapid electron transfer and more active mass deposition. Vertical nanorods grown on the rGO sheet was found to maximize electrode performance with a maximum specific capacitance of 2987 Fg−1at a current density of 1 Ag−1. The asymmetric supercapacitor was fabricated with Ni–Co LDH/rGO as a positive electrode and rGO as a negative electrode, which has rendered an energy density of 39.9 Wh/kg with a power density of 1.48 kW/kg1. Based on the obtained results, the fabricated supercapacitor is envisioned to be exploited in various potential applications.
Statistical Performance Analysis and Robust Design of Paper Microfluidic Membraneless Fuel Cell With Pencil Graphite Electrodes
Authors: Rao Lanka Tata , Dubey Satish Kumar , Javed Arshad , Goel Sanket
Published: January 2020

Paper-based membraneless microfluidic fuel cell (PMMFC) has emerged as an alternative to conventional fuel cells. Extraction of optimum energy yield from these PMMFCs requires selection and study of various design and operating parameters. In this context, this paper presents reliability analysis and robust design of PMMFC composed of air-breathing graphite electrodes using multiple concentrations of formic acid and sulfuric acid as fuel and electrolyte, respectively. Combinations of four different grades of pencils are employed to prepare the electrodes using various pencil strokes. PMMFC is analyzed for two different orientations—horizontal and vertical, and the maximum power outputs were recorded. In order to analyze the combined effects of different factors governing the performance of PMMFC, a statistical approach of full factorial design is utilized to perform analysis of mean (ANOM), analysis of variance (ANOVA), signal to noise ratio (SNR), and desirability study. The response equations in terms of coded values of the factors are also derived. Rigorous desirability study, with the optimized parameters, concludes that the best desirability values for the horizontal and vertical arrangements of PMMFC are 0.8842 and 0.92768, respectively. Overall, this study helps to develop reliable, robust, and efficient PMMFC for many realistic applications.
Polyethylene glycol: Optical constants from 191 to 1688 nm (0.735–6.491 eV) by spectroscopic ellipsometry
Authors: Shah Dhruv , Roychowdhury Tuhin , Hilfiker James N. , Linford Matthew R.
Published: January 2020

Polyethylene glycol (PEG) is an important polymer with numerous industrial and therapeutic applications. Accordingly, the optical constants of PEG should be a useful resource to other scientists and engineers. Herein, we report the optical functions of PEG as determined from reflection spectroscopic ellipsometry (SE) and transmission ultraviolet-visible spectroscopy. These functions were obtained from a commercial liquid sample of PEG that had a molecular weight of 285–315 g/mol. Since this sample is a liquid, the reflection and transmission measurements required special experimental considerations. The reflection SE measurements necessitated roughening (frosting) the inside of the vessel (Petri dish) that contained PEG and leveling the instrument instead of the liquid sample. The transmission measurements were obtained via a dual-cuvette approach that removed the effects of the cuvettes and their interfaces. From these measurements, the extinction coefficient of the PEG was determined between 205 and 1700 nm. Since PEG has very low absorption over the measured wavelength range, and because of the relatively wide wavelength range considered here, the refractive index was fit with a Sellmeier model for wavelengths from 191 to 1688 nm. The interface at the liquid surface was modeled with a Bruggeman effective medium approximation. The optical functions obtained in this work agree well with previously reported values. For example, we obtained the following nx values for the material, where x is the wavelength in nanometers: n300 = 1.493, n500 = 1.459, and n1000 = 1.443.
Compliance With 24-Hour Movement Guidelines in Hong Kong Adolescents: Associations With Weight Status
Authors: Shi Yan , Huang Wendy Yajun , Sit Cindy Hui-Ping , Wong Stephen Heung-Sang
Published: January 2020

Background: This study examined the compliance with the 24-Hour Movement Guidelines among Hong Kong adolescents and its associations with body mass index (BMI). Methods: A total of 1039 adolescents (11–18 y) wore the activPAL™ for 24 hours for 7 consecutive days to assess physical activity (PA) and sleep duration. Screen time was measured using the Children’s Leisure Activities Study Survey (Chinese version). Linear mixed models were performed for analysis. Results: The analytic sample consisted of 692 adolescents (53% girls). Only 1.0% of the adolescents met all of the recommendations. The proportions of adolescents who met the recommendation for PA, screen time, and sleep were 9.1%, 31.2%, and 38.6%, respectively. Adolescent boys who did not meet the PA recommendation (β = 3.36; 95% CI, 1.04 to 5.68; P = .001) and those who did not meet the combination of PA and sleep recommendations (β = 2.10, 95% CI, 0.64 to 3.56; P = .01) had a higher body mass index than those who met the respective recommendations. Conclusions: Compliance with the 24-Hour Movement Guidelines was alarmingly low among Hong Kong adolescents. Meeting the PA recommendation or the combination of PA and sleep recommendations was associated with a healthier body weight in boys.
Structure-guided discovery of a single-domain antibody agonist against human apelin receptor
Authors: Ma Yanbin , Ding Yao , Song Xianqiang , Ma Xiaochuan , Li Xun , Zhang Ning , Song Yunpeng , Sun Yaping , Shen Yuqing , Zhong Wenge , Hu Liaoyuan A. , Ma Yingli , Zhang Mei-Yun
Published: January 2020

We converted a potent antagonistic sdAb JN241 to an agonistic sdAb JN241-9 to human APJ by structure-guided rational design.
Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion
Authors: Plemel Jason R. , Stratton Jo Anne , Michaels Nathan J. , Rawji Khalil S. , Zhang Eric , Sinha Sarthak , Baaklini Charbel S. , Dong Yifei , Ho Madelene , Thorburn Kevin , Friedman Timothy N. , Jawad Sana , Silva Claudia , Caprariello Andrew V. , Hoghooghi Vahid , Yue Julie , Jaffer Arzina , Lee Kelly , Kerr Bradley J. , Midha Raj , Stys Peter K. , Biernaskie Jeff , Yong V. Wee
Published: January 2020

Microglia respond to white matter injury with different populations that prevent macrophage dispersion into spared tissue.
The 22 December 2018 tsunami from flank collapse of Anak Krakatau volcano during eruption
Authors: Ye Lingling , Kanamori Hiroo , Rivera Luis , Lay Thorne , Zhou Yu , Sianipar Dimas , Satake Kenji
Published: January 2020

Rapid quantification of the Anak Krakatau landslide by regional seismic data could have aided in warning of the resulting tsunami.
Coherent vortex dynamics in a strongly interacting superfluid on a silicon chip
Authors: Sachkou Yauhen P. , Baker Christopher G. , Harris Glen I. , Stockdale Oliver R. , Forstner Stefan , Reeves Matthew T. , He Xin , McAuslan David L. , Bradley Ashton S. , Davis Matthew J. , Bowen Warwick P.
Published: January 2020

Following vortices around

When stirred, superfluids react by creating quantized vortices. Studying the dynamics of these vortices, especially in the strongly interacting regime, is technically challenging. Sachkou
et al.
developed a technique for the nondestructive tracking of vortices in thin films of superfluid helium-4. Their system contained a microtoroid optical cavity coated by a thin film of helium-4, in which vortices were created by using laser light. When imaging the subsequent dynamics of the vortices, the researchers found that coherent dynamics strongly dominated over dissipation.

Science
, this issue p.
1480
Are noncommunicable diseases communicable?
Authors: Finlay B. B ,   CIFAR Humans,   the Microbiome
Published: January 2020

Numerous noncommunicable diseases could have a transmissible microbial component
Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation
Authors: Wong Wing Hing , Bhatt Sima , Trinkaus Kathryn , Pusic Iskra , Elliott Kevin , Mahajan Nitin , Wan Fei , Switzer Galen E. , Confer Dennis L. , DiPersio John , Pulsipher Michael A. , Shah Nirali N. , Sees Jennifer , Bystry Amelia , Blundell Jamie R. , Shaw Bronwen E. , Druley Todd E.
Published: January 2020

Donor hematopoietic clones with pathogenic mutations engraft and persist in unrelated hematopoietic stem cell transplant recipients.
Intratumoral expression of IL-7 and IL-12 using an oncolytic virus increases systemic sensitivity to immune checkpoint blockade
Authors: Nakao Shinsuke , Arai Yukinori , Tasaki Mamoru , Yamashita Midori , Murakami Ryuji , Kawase Tatsuya , Amino Nobuaki , Nakatake Motomu , Kurosaki Hajime , Mori Masamichi , Takeuchi Masahiro , Nakamura Takafumi
Published: January 2020

Oncolytic vaccinia virus encoding IL-7 and IL-12 facilitates immune checkpoint blockade in treatment-resistant solid tumors.
Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance
Authors: Park Eugene , Chen Jingyu , Moore Andrew , Mangolini Maurizio , Santoro Antonella , Boyd Joseph R. , Schjerven Hilde , Ecker Veronika , Buchner Maike , Williamson James C. , Lehner Paul J. , Gasparoli Luca , Williams Owen , Bloehdorn Johannes , Stilgenbauer Stephan , Leitges Michael , Egle Alexander , Schmidt-Supprian Marc , Frietze Seth , Ringshausen Ingo
Published: January 2020

Inhibition of stromal cell PKC-β mitigates environment-mediated drug resistance in B cell malignancies.
β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade
Authors: Zhang Fang , Gannon Mary , Chen Yunjia , Yan Shun , Zhang Sixue , Feng Wendy , Tao Jiahui , Sha Bingdong , Liu Zhenghui , Saito Takashi , Saido Takaomi , Keene C. Dirk , Jiao Kai , Roberson Erik D. , Xu Huaxi , Wang Qin
Published: January 2020

Noradrenergic signaling sensitizes pathological GSK3β/tau activation to nanomolar Aβ.
Phase I, Dose-Escalating Study of the Safety and Pharmacokinetics of Inhaled Dry-Powder Vancomycin (AeroVanc) in Volunteers and Patients with Cystic Fibrosis: a New Approach to Therapy for Methicillin-Resistant Staphylococcus aureus
Authors: Waterer Grant , Lord John , Hofmann Thomas , Jouhikainen Taneli
Published: January 2020

Methicillin-resistant
Staphylococcus aureus
(MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administration of vancomycin would overcome these limitations, we developed a dry powder formulation suitable for inhalation (AeroVanc).
N
-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and
N
-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment
Authors: Mthiyane Thuli , Millard James , Adamson John , Balakrishna Yusentha , Connolly Cathy , Owen Andrew , Rustomjee Roxana , Dheda Keertan , McIlleron Helen , Pym Alexander S.
Published: January 2020

The distribution of
N
-acetyltransferase 2 gene (
NAT2
) polymorphisms varies considerably among different ethnic groups. Information on
NAT2
single-nucleotide polymorphisms in the South African population is limited. We investigated
NAT2
polymorphisms and their effect on isoniazid pharmacokinetics (PK) in Zulu black HIV-infected South Africans in Durban, South Africa. HIV-infected participants with culture-confirmed pulmonary tuberculosis (TB) were enrolled from two unrelated studies.
Potential Control of Potato Soft Rot Disease by the Obligate Predators
Bdellovibrio
and Like Organisms
Authors: Youdkes Daniel , Helman Yael , Burdman Saul , Matan Ofra , Jurkevitch Edouard
Published: January 2020

Bacterial soft rot diseases caused by
Pectobacterium
spp. and
Dickeya
spp. are among the most important plant diseases caused by bacteria. Among other crops, they inflict large-scale damage to potatoes. As of today, farmers have few options to control them. The bacteria
Bdellovibrio
and like organisms (BALOs) are obligate predators of bacteria. We tested their potential to prey on
Pectobacterium
spp. and
Dickeya
spp. and to protect potato. We show that different BALOs can prey on soft rot-causing bacteria and prevent their growth
in situ
, precluding tissue maceration. Dead predators and the supernatant of BALO cultures did not significantly prevent maceration, showing that the effect is due to predation. Soft rot control by the predators was concentration dependent and was higher when the predator was inoculated ahead of the prey. As residual prey remained, we investigated what determines their level and found that initial prey and predator population parameters affect prey response to predation.
Polymorphisms within the
ARNT2
and
CX3CR1
Genes Are Associated with the Risk of Developing Invasive Aspergillosis
Authors: Lupiañez C. B. , Martínez-Bueno M. , Sánchez-Maldonado J. M. , Badiola J. , Cunha C. , Springer J. , Lackner M. , Segura-Catena J. , Canet L. M. , Alcazar-Fuoli L. , López-Nevot M. A. , Fianchi L. , Aguado J. M. , Pagano L. , López-Fernández E. , Alarcón-Riquelme M. , Potenza L. , Gonçalves S. M. , Luppi M. , Moratalla L. , Solano C. , Sampedro A. , González-Sierra P. , Cuenca-Estrella M. , Lagrou K. , Maertens J. A. , Lass-Flörl C. , Einsele H. , Vazquez L. ,   PCRAGA Study Group, Loeffler J. , Ríos-Tamayo R. , Carvalho A. , Jurado M. , Sainz J.
Published: January 2020

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the
ARNT2
and
CX3CR1
genes influence the risk of IA in high-risk hematological patients.
Substrate Interaction with the EssC Coupling Protein of the Type VIIb Secretion System
Authors: Mietrach Nicole , Damián-Aparicio Diana , Mielich-Süss Benjamin , Lopez Daniel , Geibel Sebastian
Published: January 2020

The emergence of antibiotic-resistant bacteria poses a rising problem in antibiotic treatment (S. Boyle-Vavra and R. S. Daum, Lab Invest 87:3–9, 2007,
https://doi.org/10.1038/labinvest.3700501
). We have used the multidrug-resistant
S. aureus
USA300_FPR3757 as a model organism to study the T7SSb. Effector proteins of this system have been associated with abscess formation and bacterial persistence in mouse models (M. L. Burts, A. C. DeDent, and D. M. Missiakas, Mol Microbiol 69:736–746, 2008,
https://doi.org/10.1111/j.1365-2958.2008.06324.x
; M. L. Burts, W. A. Williams, K. DeBord, and D. M. Missiakas, Proc Natl Acad Sci U S A 102:1169–1174, 2005,
https://doi.org/10.1073/pnas.0405620102
). We determined the structure of the essential ATPase domain D3 of the T7SSb at atomic resolution and validated a surface-exposed pocket as a potential drug target to block secretion. Furthermore, our study provides new mechanistic insights into the T7SSb substrate transport.
Differentiation of Francisella tularensis Subspecies and Subtypes
Authors: Larson Marilynn A. , Sayood Khalid , Bartling Amanda M. , Meyer Jennifer R. , Starr Clarise , Baldwin James , Dempsey Michael P.
Published: January 2020

The highly infectious and zoonotic pathogen
Francisella tularensis
is the etiologic agent of tularemia, a potentially fatal disease if untreated. Despite the high average nucleotide identity, which is >99.2% for the virulent subspecies and >98% for all four subspecies, including the opportunistic microbe
Francisella tularensis
subsp.
novicida
, there are considerable differences in genetic organization. These chromosomal disparities contribute to the substantial differences in virulence observed between the various
F. tularensis
subspecies and subtypes.
Single-Locus-Sequence-Based Typing of the
mgpB
Gene Reveals Transmission Dynamics in Mycoplasma genitalium
Authors: Fernández-Huerta Miguel , Serra-Pladevall Judit , Esperalba Juliana , Moreno-Mingorance Albert , Fernández-Naval Candela , Barberá María-Jesús , Aparicio David , Pich Oscar Q. , Pumarola Tomàs , Jensen Jorgen S. , Espasa Mateu
Published: January 2020

Sexually transmitted infections (STIs) by
Mycoplasma genitalium
are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of
M. genitalium
and the epidemiology of antimicrobial resistance. This
mgpB
-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively.
Autologous Antibody Responses to an HIV Envelope Glycan Hole Are Not Easily Broadened in Rabbits
Authors: Yang Yuhe R. , McCoy Laura E. , van Gils Marit J. , Andrabi Raiees , Turner Hannah L. , Yuan Meng , Cottrell Christopher A. , Ozorowski Gabriel , Voss James , Pauthner Matthias , Polveroni Thomas M. , Messmer Terrence , Wilson Ian A. , Sanders Rogier W. , Burton Dennis R. , Ward Andrew B.
Published: January 2020

A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer-immunized rabbits. Our high-resolution cryo-electron microscopy (cryoEM) studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing prime-boost immunogens remains difficult.
Middle and late Pleistocene pluvial history of Newark Valley, central Nevada, USA
Authors: Redwine Joanna R. , Burke R.M. , Reheis M.C. , Bowers R.J. , Bright J. , Kaufman D.S. , Forester* R.M.
Published: January 2020

Newark Valley lies between the two largest pluvial lake systems in the Great Basin, Lake Lahontan and Lake Bonneville. Soils and geomorphology, stratigraphic interpretations, radiocarbon ages, and amino acid racemization geochronology analyses were employed to interpret the relative and numerical ages of lacustrine deposits in the valley. The marine oxygen isotope stage (MIS) 2 beach barriers are characterized by well-preserved morphology and deposits with youthful soil development, with Bwk horizons and maximum stage I+ carbonate morphology. Radiocarbon ages of gastropods and tufas within these MIS 2–age deposits permit construction of a latest Pleistocene lake-level curve for Newark Valley, including a maximum limiting age of 13,780 ± 50 14C yr B.P. for the most recent highstand, and they provide a calibration point for soil development in lacustrine deposits in the central Great Basin. The MIS 8–age to MIS 4–age beach barriers are higher in elevation and represent a larger lake than existed during MIS 2. The beach barriers have subdued morphology, are only preserved in short segments, and have stronger soil development, with Bkm and/or Bkmt horizons and maximum stage III+ to IV carbonate morphology. Newark Lake reached elevations higher than the MIS 2 highstand during at least two additional pluvial periods, MIS 16 and MIS 12, 10, or 8. These oldest lacustrine deposits do not have preserved shoreline features and are represented only by gravel lags, buried deposits, and buried soils with similar strong soil development. This sequence of middle and latest Pleistocene shorelines records a long-term pluvial history in this basin that remained internally drained for the last four or more pluvial cycles.

Obtaining numerical ages from material within lacustrine deposits in the Great Basin can be challenging. Amino acid D/L values from gastropod shells and mollusk valves proved to be a valuable tool to correlate lacustrine deposits within Newark Valley. Comparison of soils and geomorphology results to independent 36Cl cosmogenic nuclide ages from a different study indicated unexpected changes in rates of soil development during the past ~200,000 yr and suggested that common stratigraphic changes in lake stratigraphy could obscure incremental changes in soil development and/or complicate 36Cl cosmogenic nuclide age estimates.
A new stratigraphic framework and constraints for the position of the Paleocene–Eocene boundary in the rapidly subsiding Hanna Basin, Wyoming
Authors: Dechesne Marieke , Currano Ellen D. , Dunn Regan E. , Higgins Pennilyn , Hartman Joseph H. , Chamberlain Kevin R. , Holm-Denoma Christopher S.
Published: January 2020

The Paleocene–Eocene strata of the rapidly subsiding Hanna Basin give insights in sedimentation patterns and regional paleogeography during the Laramide orogeny and across the climatic event at the Paleocene–Eocene Thermal Maximum (PETM). Abundant coalbeds and carbonaceous shales of the fluvial, paludal, and lacustrine strata of the Hanna Formation offer a different depositional setting than PETM sections described in the nearby Piceance and Bighorn Basins, and the uniquely high sediment accumulation rates give an expanded and near-complete record across this interval. Stratigraphic sections were measured for an ∼1250 m interval spanning the Paleocene–Eocene boundary across the northeastern syncline of the basin, documenting depositional changes between axial fluvial sandstones, basin margin, paludal, floodplain, and lacustrine deposits. Leaf macrofossils, palynology, mollusks, δ13C isotopes of bulk organic matter, and zircon sample locations were integrated within the stratigraphic framework and refined the position of the PETM. As observed in other basins of the same age, an interval of coarse, amalgamated sandstones occurs as a response to the PETM. Although this pulse of relatively coarser sediment appears related to climate change at the PETM, it must be noted that several very similar sandstone bodies occur with the Hanna Formation. These sandstones occur in regular intervals and have an apparent cyclic pattern; however, age control is not sufficient yet to address the origin of the cyclicity. Signs of increased ponding and lake expansion upward in the section appear to be a response to basin isolation by emerging Laramide uplifts.
Retinal vessel diameter changes after 6 months of treatment in the Idiopathic Intracranial Hypertension Treatment Trial
Authors: Moss Heather E , Hollar Rachel A , Fischer William S , Feldon Steven E
Published: January 2020

Background/Aims

Prior studies support an association between increased retinal venule diameter and elevated intracranial pressure (ICP). The purpose of this study was to test the hypothesis that retinal venule diameters decrease in association with long-term therapy for high ICP in subjects with idiopathic intracranial hypertension (IIH).

Methods

This is a retrospective analysis of multicentre randomised controlled trial data. Standardised procedures were used to measure area of optic nerve head elevation (ONHA) and diameters of 4 arterioles and 4 venules 2.7 mm from the optic disc centre on fundus photos collected at baseline and after 6 months of randomised treatment with placebo+diet or acetazolamide+diet in subjects participating in the IIH Treatment Trial (IIHTT) (n=115). Change in arteriole (Da) and venule (Dv) diameters from baseline to 6 months was studied as a function of IIH, haemodynamic and demographic variables.

Results

Dv decreased following 6 months of therapy (8.1 µm, 5.9%, p<0.0005) but Da did not change. Dv change was associated with ONHA change (p<0.0005, r=0.47) and this association persisted in multiple variable models.

Conclusions

Retinal venule diameter decreased, and arteriole diameter did not change in association with treatment for elevated ICP with a weight loss intervention and placebo or acetazolamide in IIHTT participants. Further study is needed to determine how retinal vessel measurements can be combined with other clinical observations to inform disease management.
Conjunctival lymphangiectasia as a biomarker of severe systemic disease in Ser77Tyr hereditary transthyretin amyloidosis
Authors: Bunod Roxane , Adams David , Cauquil Cécile , Francou Bruno , Labeyrie Céline , Bourenane Halima , Adam Clovis , Algalarrondo Vincent , Slama Michel , Darce-Bello Martha , Barreau Emmanuel , Labetoulle Marc , Rousseau Antoine
Published: January 2020

Aims

To investigate the relationship between the ophthalmic and systemic phenotypes in patients with hereditary transthyretin amyloidosis with the S77Y mutation (ATTRS77Y).

Methods

In this cross-sectional study, patients with genetically confirmed ATTRS77Y amyloidosis were enrolled. All patients underwent complete neurological examination, including staging with the Neuropathy Impairment Score (NIS), Polyneuropathy Disability (PND) score; complete cardiological evaluation, including echocardiography, cardiac MRI and/or cardiac scintigraphy and complete ophthalmic evaluation, including slit lamp examination and fundus examination. Ocular ancillary tests (fluorescein and indocyanine green angiography, and anterior segment optical coherence tomography) were performed in cases with abnormal findings. The Kruskal-Wallis test was used for quantitative outcomes and Fisher’s exact test for qualitative outcomes. Statistical significance was indicated by p<0.05 (two tailed).

Results

The study sample was composed of 24 ATTRS77Y patients. The mean patient age was 58.4±12.4 years. None of the patients presented with amyloid deposits in the anterior chamber, secondary glaucoma or vitreous amyloidosis. Retinal angiopathy was observed in four patients, complicated with retinal ischaemia in one patient. Conjunctival lymphangiectasia (CL) was detected in 13 patients (54%), associated with perilymphatic amyloid deposits. The presence of CL was statistically associated with more severe neurological disease (NIS=43.3±31.9 vs 18.9±20.4; PND=2.6±1.0 vs 1.4±0.7 in patients with and without CL, respectively; both p<0.05) and amyloid cardiomyopathy (p=0.002).

Conclusion

In ATTRS77Y patients, CL is common and could serve as a potential biomarker for severe systemic disease. There were neither anterior chamber deposits, secondary glaucoma nor vitreous deposits in ATTRS77Y patients.
The effect of eHealth-based falls prevention programmes on balance in people aged 65 years and over living in the community: protocol for a systematic review of randomised controlled trials
Authors: Ambrens Meghan , Tiedemann Anne , Delbaere Kim , Alley Stephanie , Vandelanotte Corneel
Published: January 2020

Introduction

Between 20% and 28% of community-dwelling older people experience a fall each year. Falls can result in significant personal and socioeconomic costs, and are the leading cause of admission to hospital for an older person in Australia. Exercise interventions that target balance are the most effective for preventing falls in community-dwellers; however, greater accessibility of effective programmes is needed. As technology has become more accessible, its use as a tool for supporting and promoting health and well-being of individuals has been explored. Little is known about the effectiveness of eHealth technologies to deliver fall prevention interventions. This protocol describes a systematic review with meta-analysis that aims to evaluate the effect of eHealth fall prevention interventions compared with usual care control on balance in people aged 65 years and older living in the community.

Methods and analysis

We will perform a systematic search of the following electronic databases: MEDLINE, CINAHL Complete, Embase and PsychINFO and citation search of Scopus, Web of Science, PubMed Central, Cochrane Database Central and PEDro for randomised controlled trials that use an eHealth technology to deliver a fall prevention intervention to community-dwellers aged ≥65 years, that are published in English, and include a balance outcome (primary outcome). The screening and selection of articles for review will be undertaken by two independent reviewers. The PEDro scale and Grading of Recommendations, Assessment, Development and Evaluations will be used to assess study quality. The results will be synthesised descriptively, and if sufficient data are available and the studies are not overly heterogeneous, a meta-analysis will be conducted using the random effects model.

Ethics and dissemination

As this will be a systematic review, without involvement of human participants, there will be no requirement for ethical approval. The results of this systematic review will be disseminated through peer-reviewed publications, conference presentations and dissemination to policymakers and consumers to maximise health impact.

PROSPERO registration number

CRD42018115098.
Cost-effectiveness of total knee replacement in addition to non-surgical treatment: a 2-year outcome from a randomised trial in secondary care in Denmark
Authors: Skou Søren Thorgaard , Roos Ewa , Laursen Mogens , Arendt-Nielsen Lars , Rasmussen Sten , Simonsen Ole , Ibsen Rikke , Larsen Arendse T , Kjellberg Jakob
Published: January 2020

Objective

To assess the 24-month cost-effectiveness of total knee replacement (TKR) plus non-surgical treatment compared with non-surgical treatment with the option of later TKR if needed.

Methods

100 adults with moderate-to-severe knee osteoarthritis found eligible for TKR by an orthopaedic surgeon in secondary care were randomised to TKR plus 12 weeks of supervised non-surgical treatment (exercise, education, diet, insoles and pain medication) or to supervised non-surgical treatment alone. Including quality-adjusted life years (QALYs) data from baseline, 3, 6, 12 and 24 months, effectiveness was measured as change at 24 months. Healthcare costs and transfer payments were derived from national registries. Incremental healthcare costs, and incremental cost-effectiveness ratios (ICERs) were calculated. A probabilistic sensitivity analysis was conducted and the probability of cost-effectiveness was estimated at the 22 665 Euros/QALY threshold defined by the National Institute for Health and Care Excellence.

Results

TKR plus non-surgical treatment was more expensive (mean of 23 076 vs 14 514 Euros) but also more effective than non-surgical treatment (mean 24-month improvement in QALY of 0.195 vs 0.056). While cost-effective in the unadjusted scenario (ICER of 18 497 Euros/QALY), TKR plus non-surgical treatment was not cost-effective compared with non-surgical treatment with the option of later TKR if needed in the adjusted (age, sex and baseline values), base-case scenario (ICER of 32 611 Euros/QALY) with a probability of cost-effectiveness of 23.2%. Including deaths, TKR plus non-surgical treatment was still not cost-effective (ICERs of 46 277 to 64 208 Euros/QALY).

Conclusions

From a 24-month perspective, TKR plus non-surgical treatment does not appear to be cost-effective compared with non-surgical treatment with the option of later TKR if needed in patients with moderate-to-severe knee osteoarthritis and moderate intensity pain in secondary care in Denmark. Results were sensitive to changes, highlighting the need for further confirmatory research also assessing the long-term cost-effectiveness of TKR.

Trial registration number

ClinicalTrials.gov (NCT01410409).