bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of rainfall uncertainty on the performance of physically based rainfall–runoff models
Authors: Fraga Ignacio , Cea Luis , Puertas Jerónimo
Published: November 2018

This paper analyses the effect of rain data uncertainty on the performance of two hydrological models with different spatial structures: a semidistributed and a fully distributed model. The study is performed on a small catchment of 19.6 km2 located in the north‐west of Spain, where the arrival of low pressure fronts from the Atlantic Ocean causes highly variable rainfall events. The rainfall fields in this catchment during a series of storm events are estimated using rainfall point measurements. The uncertainty of the estimated fields is quantified using a conditional simulation technique. Discharge and rain data, including the uncertainty of the estimated rainfall fields, are then used to calibrate and validate both hydrological models following the generalized likelihood uncertainty estimation (GLUE) methodology. In the storm events analysed, the two models show similar performance. In all cases, results show that the calibrated distribution of the input parameters narrows when the rain uncertainty is included in the analysis. Otherwise, when rain uncertainty is not considered, the calibration of the input parameters must account for all uncertainty in the rainfall–runoff transformation process. Also, in both models, the uncertainty of the predicted discharges increase in similar magnitude when the uncertainty of rainfall input increase.
Mitonuclear epistasis, genotype‐by‐environment interactions, and personalized genomics of complex traits in Drosophila
Authors: Rand David M. , Mossman Jim A. , Zhu Lei , Biancani Leann M. , Ge Jennifer Y.
Published: November 2018

Mitochondrial function requires the coordinated expression of dozens of gene products from the mitochondrial genome and hundreds from the nuclear genomes. The systems that emerge from these interactions convert the food we eat and the oxygen we breathe into energy for life, while regulating a wide range of other cellular processes. These facts beg the question of whether the gene‐by‐gene interactions (G x G) that enable mitochondrial function are distinct from the gene‐by‐environment interactions (G x E) that fuel mitochondrial activity. We examine this question using a Drosophila model of mitonuclear interactions in which experimental combinations of mtDNA and nuclear chromosomes generate pairs of mitonuclear genotypes to test for epistatic interactions (G x G). These mitonuclear genotypes are then exposed to altered dietary or oxygen environments to test for G x E interactions. We use development time to assess dietary effects, and genome wide RNAseq analyses to assess hypoxic effects on transcription, which can be partitioned in to mito, nuclear, and environmental (G x G x E) contributions to these complex traits. We find that mitonuclear epistasis is universal, and that dietary and hypoxic treatments alter the epistatic interactions. We further show that the transcriptional response to alternative mitonuclear interactions has significant overlap with the transcriptional response to alternative oxygen environments. Gene coexpression analyses suggest that these shared genes are more central in networks of gene interactions, implying some functional overlap between epistasis and genotype by environment interactions. These results are discussed in the context of evolutionary fitness, the genetic basis of complex traits, and the challenge of achieving precision in personalized medicine. © 2018 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 70(12):1275–1288, 2018
FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice
Authors: Schrauwen Isabelle , Giese Arnaud PJ , Aziz Abdul , Lafont David Tino , Chakchouk Imen , Santos-Cortez Regie Lyn P , Lee Kwanghyuk , Acharya Anushree , Khan Falak Sher , Ullah Asmat , Nickerson Deborah A , Bamshad Michael J , Ali Ghazanfar , Riazuddin Saima , Ansar Muhammad , Ahmad Wasim , Ahmed Zubair M , Leal Suzanne M
Published: November 2018

Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a-/- homozygous mice also exhibit an abnormal digit morphology, including metatarsal osteomas and polysyndactyly, in addition to distinct abnormalities on the deltoid tuberosity of their humeri. In conclusion, we present a new nonsyndromic PAPA ciliopathy due to a loss-of-function variant in FAM92A. © 2018 American Society for Bone and Mineral Research.
Cardiovascular Autonomic Neuropathy as a New Complication of Postsurgical Chronic Hypoparathyroidism
Authors: Tabacco Gaia , Naciu Anda Mihaela , Maggi Daria , Santonati Assunta , Pedone Claudio , Cesareo Roberto , Bosco Daniela , Gaspa Gianluigi , Napoli Nicola , Pozzilli Paolo , Manfrini Silvia , Palermo Andrea
Published: November 2018

Postsurgical hypoparathyroidism (hypoPT) increases fatigue and seems to affect the risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system, a cause of increased mortality, and associated with increased fatigability. The aim of this study is to evaluate CAN in hypoPT and its relationship with hypocalcemia, PTH levels, and hyperphosphatemia. This is a cross-sectional study comparing 51 postsurgical hypoPT patients treated with calcium and calcitriol and 43 control subjects without any PTH/calcium/phosphate disorders who underwent thyroidectomy. CAN was assessed by heart rate (HR) response to deep breathing, HR response to the lying-to-standing test, HR response to the Valsalva maneuver, and blood pressure response to standing. Participants were considered to have “early CAN” if they had one abnormal result in the HR tests and “definite CAN” with two or more abnormal results. The prevalence of CAN was 23% in the control group and 78% in the hypoPT group (OR 11.48; 95% CI, 4.48 to 32.17). Patients with hypoPT and serum calcium (sCa) ≥8.5 mg/dL had a prevalence of early CAN of 72.4% and the prevalence was 86.4% in those with sCa <8.5 mg/dL. Definite CAN was found in 2.3% of the control group, 24.1% of the hypoPT group without hypocalcemia, and 59.1% of the hypoPT group with hypocalcemia. In the hypoPT group, the OR for definite CAN in the patients with hypocalcemia compared to the patients with normocalcemia was 4.54 (95% CI, 1.36 to 15.11). The association between low sCa and definite CAN was confirmed after adjustment for confounders with OR 13.62 (95% CI, 2.12 to 149.84). No association was found between definite CAN and PTH levels or high phosphate levels. HypoPT is associated with CAN and hypocalcemia seems to affect its severity. Larger and prospective studies are needed to confirm our findings. © 2018 American Society for Bone and Mineral Research.
Impact of bladder filling on uterine artery Doppler variables in the first trimester of pregnancy
Authors: Seravalli Viola , Masini Giulia , Morelli Chiara , Di Tommaso Mariarosaria , Pasquini Lucia , Petraglia Felice
Published: November 2018

Objective

Uterine artery (UtA) Doppler examination is used in the first trimester to assess the risk of developing preeclampsia, with a standardized technique. However, the impact of bladder filling on UtA circulatory impedance in pregnancy has not been previously studied. This study aimed to examine the effect of bladder distension on UtA‐pulsatility index (PI) and peak systolic velocity (PSV) in the first trimester of pregnancy.

Methods

The authors conducted a prospective repeated‐measure study on pregnant women presenting for first‐trimester screening for preeclampsia. Right and left UtA Doppler velocimetry was first measured with a full bladder. Bladder volume was recorded. After the patients had voided their bladder, a repeat Doppler measurement was performed. The UtA PI and PSV were recorded on each side. The Wilcoxon signed‐rank test was used to compare UtA variables before and after bladder voiding.

Results

The authors enrolled 45 patients. Mean gestational age at exam was 12.1 weeks. When women were studied with full bladder, median UtA‐PI was 1.73 (inter‐quartile range, [IQR] 1.49, 2.28) on the right and 1.71 (1.46, 2.11) on the left side. After bladder voiding, values were 1.83 (IQR 1.58, 2.20) and 1.78 (1.40, 2.18). The difference was not statistically significant (P = .26 and 0.80). Similarly, no difference was found in UtA‐PSV before and after bladder voiding on either side (P = .22 and .70).

Conclusion

In the first‐trimester of pregnancy, bladder distension does not significantly modify uterine artery Doppler variables.
Sonographic diagnosis of thyroid metastasis from hepatocellular carcinoma
Authors: Park Ji Yeon , Yi Seong Yoon , Kwon Taejung , Baek Soo Heui , Kim Seon‐Jeong , Kwon Ki Eon , Choi Jiyoun
Published: November 2018

Metastasis to the thyroid is very rare in hepatocellular carcinoma (HCC) and only a few cases have been reported. Herein, we report a rare case of metastatic HCC to the thyroid in a 63‐year‐old man and discuss the various radiologic findings. Computed tomography (CT) revealed a heterogeneous enhancing mass that had invaded the thyroid cartilage in the left upper thyroid, compressing the airway. Ultrasonography (US) showed a heterogeneous hypoechoic mass with increased vascularity in the peripheral portion. The mass showed focal intense uptake on positron emission tomography‐computed tomography (PET‐CT). The patient underwent US‐guided core needle biopsy and the final diagnosis was metastatic HCC.
Epididymal melanotic neuroectodermal tumor of infancy: A rare cause of scrotal mass in an infant
Authors: Burton Kirsteen R. , Ngan Bo‐Yee , Navarro Oscar M.
Published: November 2018

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign neoplasm of neural crest origin more commonly seen in the craniofacial region. We report a case of MNTI of the epididymis in a 6‐month‐old male child with emphasis on the sonographic appearance which has not been previously described. In this case, the mass was inseparable from the testicle and therefore the differential diagnosis considered both extratesticular and intratesticular masses. MNTI should be added to the differential diagnosis of scrotal masses, particularly if they present in a child younger than 12 months of age.
Enhancing atrial‐specific gene expression using a calsequestrin cis‐regulatory module 4 with a sarcolipin promoter
Authors: Yoo Jimeen , Kohlbrenner Erik , Kim Okkil , Hajjar Roger J. , Jeong Dongtak
Published: November 2018

Background

Cardiac gene therapy using the adeno‐associated virus serotype 9 vector is widely used because of its efficient transduction. However, the promoters used to drive expression often cause off‐target localization. To overcome this, studies have applied cardiac‐specific promoters, although expression is debilitated compared to that of ubiquitous promoters. To address these issues in the context of atrial‐specific gene expression, an enhancer calsequestrin cis‐regulatory module 4 (CRM4) and the highly atrial‐specific promoter sarcolipin were combined to enhance expression and minimize off tissue expression.

Methods

To observe expression and bio‐distribution, constructs were generated using two different reporter genes: luciferase and enhanced green fluorescent protein (EGFP). The ubiquitous cytomegalovirus (CMV), sarcolipin (SLN) and CRM4 combined with sarcolipin (CRM4.SLN) were compared and analyzed using the luciferase assay, western blotting, a quantitative polymerase chain reaction and fluorescence imaging.

Results

The CMV promoter containing vectors showed the strongest expression in vitro and in vivo. However, the module SLN combination showed enhanced atrial expression and a minimized off‐target effect even when compared with the individual SLN promoter.

Conclusions

For gene therapy involving atrial gene transfer, the CRM4.SLN combination is a promising alternative to the use of the CMV promoter. CRM4.SLN had significant atrial expression and minimized extra‐atrial expression.
The time has come to study dynamics at work
Authors: Vantilborgh Tim , Hofmans Joeri , Judge Timothy A.
Published: November 2018

Most, if not all, workplace phenomena are dynamic, meaning that they emerge, evolve, and dissolve over time. Yet, the role of time is commonly overlooked in OB literature. This special issue showcases how a temporal process‐oriented lens can be used to study dynamics of workplace phenomena. In this editorial, we define the term dynamics, arguing that research on workplace dynamics focuses on how within‐person (or more broadly, within‐unit) processes unfold over time. Moreover, we zoom in on the diverse roles of time, illustrating the rich diversity in research on workplace dynamics, and we highlight three specific challenges for scholars wanting to pursue this line of research. We conclude that the time has come to move from a differential to a temporal and process‐oriented perspective, allowing us to understand what happens, how things happen, and why things happen at the workplace.
Association Between Flow Acceleration in the Carotid Artery and Intracranial Aneurysms
Authors: Chang Chun‐Wei , Wai Yau‐Yau , Lim Siew‐Na , Wu Tony
Published: November 2018

Objectives

In physiologic pulsatile flow, velocity acceleration is an independent factor determining wall shear stress experienced by the vascular endothelium. The purpose of this study was to evaluate Doppler indices of systolic velocity acceleration in extracranial cerebral vessels and the occurrence of intracranial aneurysms.

Methods

We reviewed medical records and 3.0‐T brain magnetic resonance imaging with 3‐dimensional time‐of‐flight magnetic resonance angiography of 1323 adults who underwent health checkups from June 2006 to November 2011, in whom 53 intracranial aneurysms were identified in 45 patients. Doppler ultrasound parameters of the carotid and vertebral arteries were analyzed in these 45 patients with aneurysms and compared with another 45 control participants matched for age and sex. We defined the maximum systolic acceleration (ACCmax) as the maximum slope of the early phase of systolic acceleration on the Doppler waveform and the maximum acceleration index (AImax) as the ratio of the ACCmax and peak systolic velocity.

Results

The Doppler analysis showed a significantly increased AImax and ACCmax in the common carotid artery (CCA), internal carotid artery, and vertebral artery in the aneurysm group. A cutoff 13.89 s−1 for the AImax of the CCA had sensitivity of 80% with a negative predictive value of 99% for intracranial aneurysms.

Conclusions

This study suggests that the AImax of the CCA with a cutoff of 13.89 s−1 may be an alternative to 3‐dimensional time‐of‐flight magnetic resonance angiography or computed tomographic angiography as a screening tool for intracranial aneurysms. Further prospective studies are needed to validate the diagnostic performance and cost‐effectiveness of these indices for screening.
Effects of Low‐Intensity Pulsed Ultrasound Therapy on the Temporomandibular Joint Complex in Conjunction With a Fixed Functional Appliance: A Prospective 3‐Dimensional Cone Beam Computed Tomographic Study
Authors: Maurya Raj Kumar , Jayan Balakrishna , Singh Harpreet , Nakra Oonit , Sharma Poonam
Published: November 2018

Objectives

This prospective study aimed to analyze 3‐dimensional changes in the temporomandibular joint (TMJ) complex with a synergistic effect of functional jaw orthopedics using a fixed functional appliance and low‐intensity pulsed ultrasound (LIPUS) therapy.

Methods

Forty patients with skeletal class II malocclusion were randomly assigned to 4 groups (2 control groups and 2 test groups) of 10 patients each. After insertion of the fixed functional appliance, the test group was stimulated with LIPUS therapy in the TMJ region bilaterally for 20 minutes daily for first 10 days and thereafter at least 3 times per week until complete mandibular advancement was achieved. Three‐dimensional images obtained with a cone beam computed tomographic scanner were used to analyze the changes in the TMJ complex at the prefunctional stage and after completion of functional appliance therapy. Direct intragroup and intergroup comparisons for different morphometric variables were conducted with the Student t test.

Results

The 40 patients included 20 male and 20 female patients between the ages of 12 and 16 years (mean age ± SD, 13.2 ± 1.8 years). Both the test groups and the control groups showed statistically significant variable changes in condylar head position and morphometric changes in relation to the joint space analysis (mean differences, –1.000 and –1.080 mm; P < .05). However, no significant differences were found during the intergroup comparisons at the prefunctional and postfunctional stages for the variables examined, except for the measurements of the linear distance of the condyle to the external auditory meatus on both the right and left sides at the prefunctional phase.

Conclusions

Low‐intensity pulsed ultrasound therapy positively affects the quantum of the joint space, thus proving to be a promising adjunct in enhancing treatment outcomes of functional jaw orthopedics in growing patients with skeletal class II malocclusions.
Detection of Concealed Uterine Prolapse in the Volume‐Rendering Mode of 4‐Dimensional Translabial Ultrasound: A Retrospective Observational Study
Authors: Wen Lieming , Li Yinbo , Qing Zhenzhen , Liu Minghui
Published: November 2018

Objectives

To assess the association between a widened vaginal canal on volume‐rendered ultrasound (US) imaging with concealed uterine prolapse.

Methods

This work was a retrospective study of 253 women who had an International Continence Society Pelvic Organ Prolapse Quantification System examination and translabial US examination. The anteroposterior diameter of the vaginal canal was measured in the rendered axial plane for all women. The widened vaginal canal was defined as an anteroposterior diameter above the 95th centile in women with normal uterine descent. The performance of the widened vaginal canal for prediction of clinical uterine prolapse was tested.

Results

Valid data from 233 women were analyzed. A mean anteroposterior diameter of 5.6 mm (range, 2.3–10.5 mm; 95th percentile, 10 mm) was seen in 119 women with normal uterine descent. An eye‐shaped vaginal canal with a mean anteroposterior diameter of 17.8 mm (range, 10.7–26.8 mm) was seen in 69 women with uterine prolapse. A widened vaginal canal was defined as an anteroposterior diameter of greater than 10 mm. Of 45 concealed uterine descents, 32 had a widened vaginal canal (ie, anteroposterior diameter > 10 mm), and 27 had clinical uterine prolapse. The κ test showed good agreement between physical and US findings (κ = 0.76; P < .001). Ultrasound findings had excellent predictive value (odds ratio, 82.3) for the diagnosis of clinical uterine prolapse.

Conclusions

An eye‐shaped vaginal canal with an anteroposterior diameter of greater than 10 mm in the rendered axial plane was a sign of uterine prolapse. This sign may be helpful for detecting concealed uterine prolapse in complex pelvic organ prolapse.
Sustainability and future food security—A global perspective for livestock production
Authors: Michalk David L. , Kemp David R. , Badgery Warwick B. , Wu Jianping , Zhang Yingjun , Thomassin Paul J.
Published: November 2018

Grasslands are the predominant forage source for grazing animals and cover more of the Earth's land than any other major vegetation type. Their values are not always recognised, and conversion to other uses is continuing at a high rate leading to greater environmental and socio‐economic problems. Overgrazing is one of the main drivers of productivity decline of grasslands, reflecting the pressures from excessive human populations and a demand for food. Some 20% of the world's grasslands are in a severely degraded state; others have suffered shifts to less‐desirable species. Biodiversity and greenhouse gas production have also been particular concerns. Estimates of productivity change all show a decline over recent decades, yet animal numbers continue to increase, particularly in the developing world. This paper critically reviews the projected demands for livestock products, driven largely by human population growth; the current health of the world's grasslands and how current livestock systems that depend on land conversion and overexploitation of grassland are inappropriate and need to be improved. Central to this argument is that small holders in the developing world will be responsible for a large amount of the future red meat production, and this can be achieved through more efficient livestock production systems using lower stocking rates. The Australian sheep industry is provided as an example of how livestock production and reduced environmental impacts can be achieved with improved efficiency. Changes will require smallholders to transition to a competitive, market‐oriented livestock industry, which will provide challenges.
A 55‐year‐old natural experiment gives evidence of the effects of changes in fire frequency on ecosystem properties in a seasonal subtropical dry forest
Authors: Kowaljow Esteban , Morales Mariano S. , Whitworth‐Hulse Juan I. , Zeballos Sebastián R. , Giorgis Melisa A. , Rodríguez Catón Milagros , Gurvich Diego E.
Published: November 2018

Fire frequency has been highlighted as an important component of fire effects on ecosystems; nevertheless, there is scarce information about how fire modulates changes in ecosystem properties, particularly for subtropical dry forests. A long‐term natural experiment and a multiscale approach were used to analyze changes in ecosystem properties in a subtropical dry forest subjected to contrasting fire regimes. Measurements were taken in two adjacent sites that had contrasting fire regimes (low/high fire frequency), and vegetation and soil analyses were combined with dendrochronological methods. Ten plots (20 × 20 m) were established in each site and soil (depth, chemical, and biological properties), and vegetation (species composition and growth of the dominant tree, Lithraea molleoides) variables were measured. Fire scars in L. molleoides were useful in determining fire history. Shrubs and grasses were more abundant in the high fire frequency site, with a high cover of the exotic grass Melinis repens, whereas trees and vines were more abundant in the low fire frequency site. Soil of the high fire frequency site tended to have lower C and nutrient content as well a significant lower depth than those of the low fire frequency site. Growth of L. molleoides individuals was lower in the high fire frequency site. Our results suggest that the long‐term effects of high fire frequency probably increase both soil loss and fire frequency in the future due to changes in plant composition, indicating that frequent burning is not a sustainable management option for this seasonal subtropical dry forest.
Quantitative assessment of vestibular otopathology in granulomatosis with polyangitis: A temporal bone study
Authors: Nogaki Taketoshi , Keskin Nevra , Azuma Takahiro , Paparella Michael M. , Nadol Joseph B. , Cureoglu Sebahattin
Published: November 2018

Objective

To investigate the temporal bone histopathology of vasculitis, especially in the vestibular organs, in granulomatosis with polyangitis (GPA).

Methods

Using light and differential interference contrast microscopy, we examined 12 human temporal bones from six deceased GPA patients and 12 histopathologically normal human temporal bones from six deceased age‐matched patients.

Results

In the GPA group, three patients had undergone tympanostomy tube placement. Two of them had suffered mixed hearing loss; one, sensorineural hearing loss; and one, conductive hearing loss. Of the 12 specimens in the GPA group, the granulation tissue invaded the round window niche in seven; cochlear hair cells were not preserved in five. Hemosiderin was deposited in the stria vascularis in eight specimens, in the ampulla or semicircular duct in 10, and in the vestibule in three. The spiral ligament showed severe loss of cellularity in two specimens. In the GPA group, type I vestibular hair cell density was significantly decreased; however, type II vestibular hair cell density did not significantly differ between the GPA group and the control group.

Conclusion

Our histopathologic findings in human temporal bone specimens of GPA patients delineated changes in the tympanic membrane, middle ear cavity, round window membrane, organ of Corti, stria vascularis, spiral ligament, ampulla, semicircular duct, and vestibule. Type I vestibular hair cell density significantly decreased in the GPA group, as compared with the control group.

Level of Evidence

N/A
Addition Homo‐ and Copolymerizations of Dicyclopentadiene and 5‐n‐Hexylnorbornene in the Presence of Pd‐N‐Heterocyclic Carbene Complexes
Authors: Wozniak Alyona I. , Bermesheva Evgeniya V. , Gavrilova Natalia N. , Ilyasov Igor R. , Nechaev Mikhail S. , Asachenko Andrey F. , Topchiy Maxim A. , Gribanov Pavel S. , Bermeshev Maxim V.
Published: November 2018

Herein for the first time addition homopolymerization of dicyclopentadiene (DCPD) and its copolymerization with 5‐n‐hexylnorbornene in the presence of different Pd‐N‐heterocyclic carbene complexes activated by a borate (Na+[B(3,5‐(CF3)2C6H5)4]− (NaBARF)) or methylaluminoxane (MAO) are investigated. It is found that systems based on Pd‐N‐heterocyclic carbene complex in combination with NaBARF or MAO are effective catalysts and a Pd‐N‐heterocyclic carbene complex/NaBARF system allows for the addition polymerization of these monomers in air. The influence of the N‐heterocyclic carbene structure, the nature of cocatalyst, and solvent on the catalyst activity of a system based on Pd‐N‐heterocyclic carbene complex are determined. The properties of the obtained addition polydicyclopentadiene (poly(DCPD)) such as thermal stability, solid‐state structure, and porosity are studied. The synthesized poly(DCPD) possesses Brunauer, Emmett, and Teller surface area as high as 155 m2 g−1 and so addition polymerization of DCPD can be considered as a single‐step and convenient way to synthesize of porous polymers from a norbornene derivative.
Highly Swellable Hydrogels from Waterborne Poly(Vinylamine‐co‐Acetamide)
Authors: Fischer Thorsten , Köhler Jens , Keul Helmut , Singh Smriti , Möller Martin
Published: November 2018

Hydrogels consisting of a hydrophilic polymer backbone are attractive candidates for the formation of superabsorbent hydrogels (SHs). Mainly, such hydrogels are prepared via free radical polymerization. Herein, poly(N‐vinylamine‐co‐N‐vinylacetamide) [P(VAm‐co‐NVA)] with different amine‐to‐amide ratios are crosslinked with phenyl carbonate telechelic poly(ethylene glycol) (PC‐PEG‐PC) to form a hydrogel in the presence of a base. The structure property relationship in terms of the amide‐to‐amine ratio, the carbonate‐to‐amine ratio, and the base‐to‐amine ratio is investigated by swelling experiments and rheology.13C NMR is used to determine the degree of crosslinking which can further influence the swelling behavior and the mechanical properties of the gels. The maximum swelling ratio of the hydrogels is found to be 97 000% with respect to the dry gel, with a storage modulus of 4 kPa of the as‐prepared gel. This swelling behavior of the obtained gels is above the state of the art and has a possibility to be tuned further.
Dual‐Stimuli‐Responsive Paclitaxel Delivery Nanosystems from Chemically Conjugate Self‐Assemblies for Carcinoma Treatment
Authors: Xu Jing‐Wen , Ge Xin , Lv Li‐Hua , Xu Feng , Luo Yan‐Ling
Published: November 2018

Diselenide‐bond‐linked poly(N‐isopropylacrylamide)‐paclitaxel chemical conjugates are synthesized as a drug release carrier. The conjugates can self‐assemble into “core–shell” nanoscaled micelles in aqueous solution and show thermal and redox dual‐responsiveness. The conjugates can afford a high encapsulation efficiency of up to 72.3%, and deliver hydrophobic anticancer drug paclitaxel in a temperature and oxidization or reduction stress‐mode. The in vitro 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and in vivo anticancer assays are performed to assess the cytotoxicity and anticancer activity of the conjugates, suggesting that the developed conjugates can be used to treat carcinoma as a novel and highly efficient drug delivery system.
Familial NEDD4L variant in periventricular nodular heterotopia and in a fetus with hypokinesia and flexion contractures
Authors: Elbracht Miriam , Kraft Florian , Begemann Matthias , Holschbach Petra , Mull Michael , Kabat Ildiko M. , Müller Britta , Häusler Martin , Kurth Ingo , Hehr Ute
Published: November 2018

Background

Mutations in the HECT domain of NEDD4L have recently been identified in a cohort of eight patients with a syndromic form of bilateral periventricular nodular heterotopia (PVNH) in association with neurodevelopmental delay, cleft palate, and toe syndactyly (PVNH7).

Methods

Case report based on NGS sequencing.

Results

Here, we describe a girl with a novel heterozygous NEDD4L missense variant, p.Tyr679His, and characteristic clinical findings, including bilateral periventricular nodular heterotopia, cleft palate and mild toe syndactyly. Molecular testing from peripheral blood identified the healthy father to carry the NEDD4L variant in mosaic state. Notably, a previous pregnancy of the couple had been terminated due to a complex fetal developmental disorder, including hypokinesia and flexion contractures. Upon review, this affected fetus was also shown to carry the familial NEDD4L variant.

Conclusion

Our findings may suggest a broader spectrum of NEDD4L‐associated phenotypes, including severe prenatal neurodevelopmental manifestations, which might represent yet another genetic form of fetal hypokinesia with flexion contractures.
Risk perception before and after presymptomatic genetic testing for Huntington's disease: Not always what one might expect
Authors: Stuttgen Kelsey , Dvoskin Rachel , Bollinger Juli , McCague Allison , Shpritz Barnett , Brandt Jason , Mathews Debra
Published: November 2018

Background

In 1983, Huntington's disease (HD) was the first genetic disease mapped using DNA polymorphisms. Shortly thereafter, presymptomatic genetic testing for HD began in the context of two research studies. One of these trials was at the Johns Hopkins University Huntington's Disease Center.

Methods

As part of the protocol, risk perception (RP) values were collected at 16 time points before and after testing. The current study investigated changes in RP scores before and after genetic testing. Of the 186 participants with pre‐ and post‐testing RP values, 39 also had contemporaneous research clinic notes and recent semi‐structured interviews available for analysis.

Results

The data reveal tremendous diversity in RP. While the RP scores of most individuals change in the way one would expect, 27% of participants demonstrated unexpected changes in RP after disclosure. A significantly higher proportion of individuals who received an expanded repeat result had unexpected changes in RP, compared with those who received normal repeat results.

Conclusions

The data suggest that individuals’ RP is influenced by more than merely the results of genetic testing. This finding is important for genetic counselors and healthcare providers, as it suggests that even comprehensive patient education and disclosure of genetic test results may not ensure that people fully appreciate their disease risk.
CTC1 mutations in a Brazilian family with progeroid features and recurrent bone fractures
Authors: Sargolzaeiaval Forough , Zhang Jiaming , Schleit Jennifer , Lessel Davor , Kubisch Christian , Precioso Debora R. , Sillence David , Hisama Fuki M. , Dorschner Michael , Martin George M. , Oshima Junko
Published: November 2018

Background

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC) is an autosomal recessive disorder caused by pathogenic variants of the conserved telomere maintenance component 1 (CTC1) gene. The CTC1 forms the telomeric capping complex, CST, which functions in telomere homeostasis and replication.

Methods

A Brazilian pedigree and an Australian pedigree were referred to the International Registry of Werner Syndrome (Seattle, WA, USA), with clinical features of accelerated aging and recurrent bone fractures. Whole exome sequencing was performed to identify the genetic causes.

Results

Whole exome sequencing of the Brazilian pedigree revealed compound heterozygous pathogenic variants in CTC1: a missense mutation (c.2959C>T, p.Arg987Trp) and a novel stop codon change (c.322C>T, p.Arg108*). The Australian patient carried two novel heterozygous CTC1 variants, c.2916G>T, p.Val972Gly and c.2926G>T, p.Val976Phe within the same allele. Both heterozygous variants were inherited from the unaffected father, excluding the diagnosis of CRMCC in this pedigree. Cell biological studies demonstrated accumulation of double strand break foci in lymphoblastoid cell lines derived from the patients. Increased DSB foci were extended to non‐telomeric regions of the genome, in agreement with previous biochemical studies showing a preferential binding of CTC1 protein to GC‐rich sequences.

Conclusion

CTC1 pathogenic variants can present with unusual manifestations of progeria accompanied with recurrent bone fractures. Further studies are needed to elucidate the disease mechanism leading to the clinical presentation with intra‐familial variations of CRMCC.
Minnesota organizations honored for becoming tobacco‐free
Authors: Canady Valerie A.
Published: November 2018

Recognizing the significance of addressing tobacco as a social justice issue, a handful of mental health organizations in Minnesota are being honored for their work going tobacco‐free and offering tobacco treatment support to consumers with mental illness and substance use disorders.
A vertex‐centered and positivity‐preserving scheme for anisotropic diffusion equations on general polyhedral meshes
Authors: Su Shuai , Dong Qiannan , Wu Jiming
Published: November 2018

We propose a new nonlinear positivity‐preserving finite volume scheme for anisotropic diffusion problems on general polyhedral meshes with possibly nonplanar faces. The scheme is a vertex‐centered one where the edge‐centered, face‐centered, and cell‐centered unknowns are treated as auxiliary ones that can be computed by simple second‐order and positivity‐preserving interpolation algorithms. Different from most existing positivity‐preserving schemes, the presented scheme is based on a special nonlinear two‐point flux approximation that has a fixed stencil and does not require the convex decomposition of the co‐normal. More interesting is that the flux discretization is actually performed on a fixed tetrahedral subcell of the primary cell, which makes the scheme very easy to be implemented on polyhedral meshes with star‐shaped cells. Moreover, it is suitable for polyhedral meshes with nonplanar faces, and it does not suffer the so‐called numerical heat‐barrier issue. The truncation error is analyzed rigorously, while the Picard method and its Anderson acceleration are used for the solution of the resulting nonlinear system. Numerical experiments are also provided to demonstrate the second‐order accuracy and well positivity of the numerical solution for heterogeneous and anisotropic diffusion problems on severely distorted grids.
An intelligent power manager with energy harvesting for internet of things applications
Authors: Hsieh Jian‐Yu , Chen Wei‐Ting , Lee Jen‐Ting
Published: November 2018

An intelligent power manager with solar and wireless energy harvesting for internet of things (IoT) applications has been realized. The intelligent power manager can detect the power consumption of the wearable devices and upload it to the database through the Wi‐Fi module. And then the stored data of the power consumption can be accessed by using the app of the portable devices. The solar and wireless energy harvesting has been introduced for extending the battery life of the machines. The measured conversion efficiency of the rectifier in the intelligent power manager is 23%. And the measured power consumption of the intelligent power manager is 190 mW.
A correlated noise calibration source for the internal calibration of a fully polarimetric radiometer
Authors: Oh Myeonggeun , Kim Yong‐Hoon
Published: November 2018

A novel microwave calibration source for a fully polarimetric radiometer (FPoR) is proposed for internal calibration by the electrical operation instead of a mechanical structure at S‐band. The proposed correlated noise calibration source (CNCS) using microwave components can generate vertical and horizontal polarized signals; additionally, linearly and circularly polarized signals (third and fourth Stokes parameters) are also estimated by injecting correlated noise. In contrast to existing mechanical calibration sources, this calibration source can be designed by miniaturization. Based on measured quantities under realistic conditions, the uncertainty was evaluated according to the states of the SPDT switches and phase shifters of the CNCS.
Simple auto‐calibrated gradient delay estimation from few spokes using Radial Intersections (RING)
Authors: Rosenzweig Sebastian , Holme H. Christian M. , Uecker Martin
Published: November 2018

Purpose

To develop a simple and robust tool for the estimation of gradient delays from highly undersampled radial k‐space data.

Theory

In radial imaging gradient delays induce parallel and orthogonal trajectory shifts, which can be described using an ellipse model. The intersection points of the radial spokes, which can be estimated by spoke‐by‐spoke comparison of k‐space samples, distinctly determine the parameters of the ellipse. Using the proposed method (RING), these parameters can be obtained using a least‐squares fit and utilized for the correction of gradient delays.

Methods

The functionality and accuracy of the proposed RING method is validated and compared to correlation‐based gradient‐delay estimation from opposing spokes using numerical simulations, phantom and in vivo heart measurements.

Results

In all experiments, RING robustly provides accurate gradient delay estimations even for as few as three radial spokes.

Conclusions

The simple and straightforward to implement RING method provides accurate gradient delay estimation for highly undersampled radial imaging.
Noninvasive quantification of fibrosis in skeletal and cardiac muscle in mdx mice using EP3533 enhanced magnetic resonance imaging
Authors: Murphy Alexander Peter , Greally Elizabeth , O’Hogain Dara , Blamire Andrew , Caravan Peter , Straub Volker
Published: November 2018

Purpose

Duchenne muscular dystrophy (DMD) is a genetic condition caused by mutations in the DMD gene leading to muscle degeneration, fatty replacement of muscle cells and fibrosis. A major obstacle to advancing therapeutic research into muscular dystrophies is development of sensitive, noninvasive outcome measures. To date, no validated method to noninvasively quantify fibrosis within skeletal muscle exists. EP3533 is a gadolinium‐based MRI contrast agent with an affinity to collagen‐1. The purpose of this study was to determine whether EP3533‐enhanced MRI could quantify fibrosis in a murine model of DMD (mdx) in muscle.

Methods

Mdx (n = 8) and control mice (BL10; n = 5) underwent contrast‐enhanced MRI acquisitions with EP3533. T1 mapping pre‐ and postcontrast was performed in skeletal and cardiac muscle. Post‐MRI the tibialis anterior (TA) and gastrocnemius (GCN) muscles and the heart were removed for fibrosis quantification by means of Masson’s trichrome staining and the hydroxyproline assay.

Results

Significant differences in postcontrast R1 were demonstrated between mdx and BL10 mice using EP3533 (cardiac P = 0.02, GCN P = 0.04, TA P = 0.04). Change in R1 from baseline following EP3533 administration correlated strongly to hydroxyproline levels (GCN: r = 0.83, P = 0.001; TA: r = 0.73, P = 0.01).

Conclusions

This study provides evidence for the suitability of EP3533 in the quantification of muscular fibrosis in mdx mice and demonstrated that EP3533‐derived measurements correlated strongly to ex vivo fibrosis measurement.
Propagation of Eastern Hellbenders Cryptobranchus alleganiensis alleganiensis in a Recirculating Aquaculture System at Shepherd of the Hills State Fish Hatchery
Authors: Civiello James A , Bruce Timothy J , Brisco Stuart J , Briggler Jeffrey T
Published: November 2018

The hellbender Cryptobranchus alleganiensis is an endangered aquatic salamander inhabiting coldwater streams within the Ozark Highlands of Missouri. Over the past few decades, there has been a severe decline in the populations of the two subspecies of hellbender in this region—the Eastern hellbender C. a. alleganiensis and the Ozark hellbender C. a. bishopi—accompanied by little to no recruitment of young age-classes; projections now call for negative long-term population growth for both subspecies. Captive propagation is thus considered essential for the long-term recovery of this species in Missouri, along with addressing the causes for its decline in the wild. Since 2007, Shepherd of the Hills Fish Hatchery has been the primary rearing facility in Missouri for the early life stages of Eastern hellbenders. This facility has focused on hatching fertilized eggs collected from the wild and rearing animals for repatriation into their natal streams. This paper describes the recirculating aquaculture system used to rear Eastern hellbenders, the culture techniques that have been developed, and some of the results.
Oral health and obesity in the SAYCARE study: reliability and internal validity of diagnostic methods
Authors: Rando‐Meirelles M. P. M. , Sousa M. L. R. , Vale G. C. , Lages V. A. , Vásquez P. P. , Jimenez P. , Villena R. S. , Alvarez‐Paucar M. A.
Published: November 2018

Objective

The aim of this pilot study was to address the reliability, internal validity and viability of oral health methods used in the South American Youth/Child cARdiovascular and Environmental study.

Methods

South American Youth/Child cARdiovascular and Environmental study was a multicentre feasibility observational study and conducted in seven South American cities. The training sessions were performed in two steps before data collection: the first verified the inter‐rater reproducibility between the examiners of the six centres in relation to the gold standard, and the second one verified the inter‐rater reproducibility between the examiners at each centre in relation to the main rater. The diagnostic methods used were International Caries Detection and Assessment System II and Pulpal Involvement, Ulceration, Fistula and Abscess for dental caries and Periodontal Screening and Recording and Index Plaque for periodontal disease. Anthropometric variables were measured and used to calculate the body mass index and were classified according to the cut‐off points defined by the International Obesity Task Force. Cohen's kappa coefficient and proportions of agreement were calculated to report inter‐rater and intra‐rater reliability in the calibration process and pilot study.

Results

The inter‐rater weight kappa ranged from 0.78 to 0.88 and proportion of agreement from 96.07% to 98.10% for the International Caries Detection and Assessment System II and for the Periodontal Screening and Recording, 0.68 to 0.95 and 94.40% to 98.33%, respectively, in the calibration process. At the pilot study, a total of 490 children (40.8% overweight and 12.9% obese) and 364 adolescents (23.4% overweight and 4.3% obese) were examined. The prevalence of dental caries was 66% in children and 78% in adolescents, and gingival bleeding was 49% and 58.20%, respectively.

Conclusion

The results demonstrated good reliability and internal validity after the examiners were trained, as well as the feasibility of using the methods chosen for this multicentre study.
Outcome for pediatric acute promyelocytic leukemia patients at Children's Oncology Group sites on the Leukemia Intergroup Study CALGB 9710 (Alliance)
Authors: Kutny Matthew A. , Geyer Susan , Laumann Kristina M. , Gregory John , Willman Cheryl L. , Stock Wendy , Larson Richard A. , Powell Bayard L. , Feusner James H.
Published: November 2018

Background

Acute promyelocytic leukemia (APL) is a unique leukemia subtype requiring specialized treatment including all‐trans retinoic acid (ATRA). A prior report demonstrated worse outcome among young children <5 years old compared with older children.

Methods

We evaluated outcomes for pediatric patients (<18 years old; N = 83) with APL treated on North American intergroup study CALGB 9710 at Children's Oncology Group sites. Induction and consolidation included ATRA, cytarabine, and anthracyclines. Patients ≥15 years old were randomized to addition of arsenic trioxide (ATO) consolidation. All patients were randomized to ATRA maintenance with versus without oral chemotherapy.

Results

The estimated 5‐year overall survival (OS) rate was 82%, and the event‐free survival (EFS) rate was 54%. Seven patients (8.4%) died during induction due to coagulopathy. Maintenance randomization demonstrated that addition of oral chemotherapy to ATRA significantly reduced relapse rate, but difference in EFS did not reach statistical significance (P = 0.12; 5‐year rates [95% CI]: 41% [17%–64%] ATRA only vs 72% [56%–88%] ATRA plus chemotherapy). There was no difference (P = 0.93) in EFS for age <5 years versus 5–12.99 years versus 13–17.99 years (5‐year rates: 56%, 47%, and 45%, respectively). Among adolescents 15–17.99 years old in the ATO randomization, there was a significantly lower relapse risk at 5 years for those receiving ATO (0% ATO vs 44% no ATO; P = 0.02).

Conclusion

Our data demonstrate that intensified ATRA, cytarabine, and anthracycline chemotherapy is effective for pediatric APL including very young patients, but early deaths and relapses remain barriers to cure. Further improvements are likely with incorporation of ATO into pediatric APL regimens.