bluuebunny/crossref_metadata_2025 huggingface dataset:
Dendritic Fibrous Nanosilica for Catalysis, Energy Harvesting, Carbon Dioxide Mitigation, Drug Delivery, and Sensing
Authors: Maity Ayan , Polshettiwar Vivek
Published: August 2017

Morphology‐controlled nanomaterials such as silica play a crucial role in the development of technologies for addressing challenges in the fields of energy, environment, and health. After the discovery of Stöber silica, followed by that of mesoporous silica materials, such as MCM‐41 and SBA‐15, a significant surge in the design and synthesis of nanosilica with various sizes, shapes, morphologies, and textural properties has been observed in recent years. One notable invention is dendritic fibrous nanosilica, also known as KCC‐1. This material possesses a unique fibrous morphology, unlike the tubular porous structure of various conventional silica materials. It has a high surface area with improved accessibility to the internal surface, tunable pore size and pore volume, controllable particle size, and, importantly, improved stability. Since its discovery, a large number of studies have been reported concerning its use in applications such as catalysis, solar‐energy harvesting, energy storage, self‐cleaning antireflective coatings, surface plasmon resonance‐based ultrasensitive sensors, CO2 capture, and biomedical applications. These reports indicate that dendritic fibrous nanosilica has excellent potential as an alternative to popular silica materials such as MCM‐41, SBA‐15, Stöber silica, and mesoporous silica nanoparticles. This Review provides a critical survey of the dendritic fibrous nanosilica family of materials, and the discussion includes the synthesis and formation mechanism, applications in catalysis and photocatalysis, applications in energy harvesting and storage, applications in magnetic and composite materials, applications in CO2 mitigation, biomedical applications, and analytical applications.
Postbreeding elevational movements of western songbirds in Northern California and Southern Oregon
Authors: Wiegardt Andrew , Wolfe Jared , Ralph C. John , Stephens Jaime L. , Alexander John
Published: August 2017

Migratory species employ a variety of strategies to meet energetic demands of postbreeding molt. As such, at least a few species of western Neotropical migrants are known to undergo short‐distance upslope movements to locations where adults molt body and flight feathers (altitudinal molt migration). Given inherent difficulties in measuring subtle movements of birds occurring in western mountains, we believe that altitudinal molt migration may be a common yet poorly documented phenomenon. To examine prevalence of altitudinal molt migration, we used 29 years of bird capture data in a series of linear mixed‐effect models for nine commonly captured species that breed in northern California and southern Oregon. Candidate models were formulated a priori to examine whether elevation and distance from the coast can be used to predict abundance of breeding and molting birds. Our results suggest that long‐distance migrants such as Orange‐crowned Warbler (Oreothlypis celata) moved higher in elevation and Audubon's Warbler (Setophaga coronata) moved farther inland to molt after breeding. Conversely, for resident and short‐distance migrants, we found evidence that birds either remained on the breeding grounds until they finished molting, such as Song Sparrow (Melospiza melodia) or made small downslope movements, such as American Robin (Turdus migratorius). We conclude that altitudinal molt migration may be a common, variable, and complex behavior among western songbird communities and is related to other aspects of a species’ natural history, such as migratory strategy.
Changes in Olive Paste Composition During Decanter Feeding and Effects on Oil Yield
Authors: Guerrini Lorenzo , Masella Piernicola , Angeloni Giulia , Migliorini Marzia , Parenti Alessandro
Published: August 2017

In olive oil production, olive paste is fed into a decanter in order to separate the oil from solids. The decanter is usually fed by a mohno or lobe pump. In this study, we analyze the composition of olive paste and pomace at the beginning, middle, and end of decanter feeding. The results show a change in paste composition with the two types of pumps. In both cases, olive paste contains a higher percentage of water and oil at the beginning of decanter feeding than at the end. This phenomenon is probably related to the different viscosity of the three components in the system. Furthermore, as the level for the recovery of olive oil is fixed, the change in the solid/liquid ratio causes product loss. This loss is demonstrated and quantified through the measurement of pomace oil content. Practical Applications: The paper quantifies the effect of the olive paste transport from malaxers to decanter on the olive oil yield. The transport causes a change in the relative composition among oil, water, and solids. The decanter centrifuge is not able to separate efficiently paste with different compositions. This causes marked product losses. The presented data could lead to the development of a control system able to limit the losses.

In this study the ratio of solids, water and oil in the olive paste at the beginning, middle, and end of decanter feeding are tested. Change in paste composition with the two types of pumps. Olive paste contains a higher percentage of water and oil at the beginning of decanter feeding than at the end. The level for the recovery of oil is fixed and the change in the ratio causes product loss that is quantified through the measurement of pomace oil content.
Brønsted Acid Catalyzed Domino Aza‐Piancatelli Rearrangement/Michael Reaction: Construction of 1,4‐Benzodiazepin‐5‐ones in One Pot
Authors: Nayani Kiranmai , Cinsani Radhika , Hussaini SD Anwar , Mainkar Prathama S. , Chandrasekhar Srivari
Published: August 2017

A para‐toluenesulfonic acid (pTSA) catalyzed domino aza‐Piancatelli rearrangement/Michael reaction was developed for the construction of 1,4‐benzodiazepin‐5‐ones in one pot. The method proceeds well in the presence of various furfurylcarbinols and o‐aminobenzamides to give products that contain medicinally relevant chemical entities.
A Hydrogen–Bromate Flow Battery for Air‐Deficient Environments
Authors: Modestov Alexander D. , Konev Dmitry V. , Tripachev Oleg V. , Antipov Anatoly E. , Tolmachev Yury V. , Vorotyntsev Mikhail A.
Published: August 2017

A concept of high energy density (ED) hydrogen–bromate flow battery was supported by experiments with flow cells with 0.1 to 50 cm2 apparent areas. H2/NaBrO3 flow cells with H2 gas diffusion anode, proton exchange membrane (PEM), and carbonaceous flow‐by or flow‐through cathodes were employed. Estimates show that the theoretical ED of the H2/bromate flow battery (HBFB) exceeds the ED of H2/O2 fuel cells (FC) in air‐deficient environments. At the cathode of the HBFB, aqueous, concentrated bromate (non‐toxic, and stable) is reduced to bromide by a six‐electron process. 100 % conversion of BrO3− to Br− can be achieved. Although acidification of the BrO3− electrolyte is a prerequisite, the acid concentration in the electrolyte feed can be optimized as a trade‐off between area specific power (P) of the HBFB and its complexity.
An approach for shake table performance evaluation during repair and retrofit actions
Authors: Trautner Christopher , Zheng Yewei , McCartney John S. , Hutchinson Tara
Published: August 2017

Large‐scale, servo‐hydraulic shake tables are a central fixture of many earthquake engineering and structural dynamics laboratories. Wear and component failure from frequent use may lead to control problems resulting in reduced motion fidelity, necessitating repairs and replacement of major components. This paper presents a methodology to evaluate shake table performance pre‐ and post‐repair, including the definition of important performance metrics. The strategy suggested is presented in the context of the rebuilding of a 4.9 × 3.1 m, 350‐kN‐capacity uniaxial shake table. In this case, the rebuild consisted of characterization of wear to table components, replacement of worn bearing surfaces, and replacement of hydraulic accumulators. To assess the effectiveness of the repair actions, sinusoidal and triangular waves, white noise, and earthquake histories were run on the table before and after the rebuild. The repair actions were successful in reducing the position and velocity dependence of friction, improving the ability of control algorithms to accurately reproduce earthquake motions. The maximum and average response spectral misfits in the period range of 0.1–2 seconds were reduced from approximately 50% to 15%, and from 5% to less than 2.5%, respectively.
Naringenin inhibits osteoclastogenesis through modulation of helper T cells‐secreted IL‐4
Authors: Wang Wengang , Li Mingjun , Luo Ming , Shen Mingkui , Xu Chen , Xu Genzhong , Chen Yaokun , Xia Lei
Published: August 2017

Naringenin (NAR) is a natural predominant flavanone and has a wide range of pharmacological activities. The aim of this study was to investigate the protective mechanisms of NAR on RANKL‐induced osteoclastogenesis and osteoclast bone resorption. T cells were divided into four groups under different concentrations of NAR (0, 25, 50, 100 µM). CD4+ T cell subsets in different groups were evaluated by flow cytometry. TRAP staining, pit formation assays and F‐actin ring immunofluorescent staining were performed. In addition, gene expression of osteoclast‐specific markers was analyzed by qPCR and Western blot. Our results showed that compared with the control group, there were relatively fewer Th1 and Th17 cells and more Th2 cells and Treg cells in the NAR groups. Besides, the number of TRAP‐positive multinucleated osteoclasts, the areas of bone resorption pits and the size and number of F‐actin rings were notably decreased in the bone marrow macrophages (BMMs) treated with T‐cell supernatant containing NAR. Moreover, NAR treatment dramatically reduced the expressions of cathepsin K, c‐Fos, DC‐STAMP, NFATc1, TRAP, and V‐ATPase d2 at mRNA and protein levels. However, these effects were abolished by adding a neutralizing antibody against IL‐4. In conclusion, NAR suppressed RANKL‐induced osteoclastogenesis and osteoclast bone resorption by promoting the release of IL‐4 from T cells.
Osteocalcin‐dependent regulation of glucose metabolism and fertility: Skeletal implications for the development of insulin resistance
Authors: Tangseefa Pawanrat , Martin Sally K. , Fitter Stephen , Baldock Paul A. , Proud Christopher G. , Zannettino Andrew C. W.
Published: August 2017

The skeleton has recently emerged as a critical insulin target tissue that regulates whole body glucose metabolism and male reproductive function. While our understanding of these new regulatory axes remains in its infancy, the bone‐specific protein, osteocalcin, has been shown to be centrally involved. Undercarboxylated osteocalcin acts as a secretagogue in a feed‐forward loop to stimulate pancreatic β‐cell proliferation and insulin secretion, improve insulin sensitivity, and promote testosterone production. Importantly, dysregulation of insulin signaling in bone causes a reduction in serum osteocalcin levels that is associated with elevated blood glucose and reduced serum insulin levels, suggesting that the skeleton may play a significant role in the development of diet‐induced insulin resistance. Insulin signaling is negatively regulated by the mammalian target of rapamycin complex 1 (mTORC1) which becomes hyper‐activated in response to nutrient overload. Loss‐ and gain‐of function models suggest that mTORC1 function in bone is essential for normal skeletal development; however, the role of this complex in the regulation of glucose metabolism remains to be determined. This review highlights our current understanding of the role played by osteocalcin in the skeletal regulation of glucose metabolism and fertility. In particular, it examines data emerging from transgenic mouse models which have revealed a pancreas‐bone‐testis regulatory axis and discusses recent human studies which seek to corroborate findings from mouse models with clinical observations. Moreover, we review recent studies which suggest dysregulation of insulin signaling in bone leads to the development of insulin resistance and discuss the potential role of mTORC1 signaling in this process.
Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment
Authors: Kato Manabu , Tajima Naoyuki , Shimizu Takako , Sugihara Masahiro , Furihata Kenichi , Harada Kazuhiro , Ishizuka Hitoshi
Published: August 2017

Mirogabalin (DS‐5565) is a novel preferentially selective α2δ‐1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open‐label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end‐stage renal disease (ESRD)]) were enrolled and completed the study. The AUClastincreased with severity of renal impairment; the geometric least‐squares mean ratios of AUClastcompared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUClastincrease, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment‐related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD.
Do sex reversal procedures differentially affect agonistic behaviors and sex steroid levels depending on the sexual genotype in Nile tilapia?
Authors: Gennotte Vincent , Akonkwa Balagizi , Mélard Charles , Denoël Mathieu , Cornil Charlotte A. , Rougeot Carole
Published: August 2017

In Nile tilapia Oreochromis niloticus, phenotypic males and females with different sexual genotypes (XX, XY, YY) have particular behavioral and physiological traits. Compared to natural XX females and XY males, XY and YY females and XX males expressed higher level of aggressiveness that could be related to higher levels of 17β‐estradiol and 11‐ketotestosterone, respectively. Our results suggest that the presence of a Y chromosome increases aggressiveness in females. However, since the same relationship between aggressiveness and the Y chromosome is not observed in males, we can hypothesize that the differences in aggressiveness are not directly dependent on the genotype but on the sex reversal procedures applied on young fry during their sexual differentiation to produce these breeders. These hormonal treatments could have permanently modified the development of the brain and consequently influenced the behavior of adults independently of their genotype. In both hypotheses (genotype or sex reversal influence), the causes of behavioral modifications have to be searched in an early modification of the brain sexual differentiation.
Interactive effects of parental age on offspring fitness and age‐assortative mating in a wild bird
Authors: Bowers Emerson Keith , Sakaluk Scott K. , Thompson Charles F.
Published: August 2017

Variation in parental age can have important consequences for offspring fitness and the structure of populations and disease transmission. However, our understanding of the effects of parental age on offspring in natural populations is limited. Here, we investigate consequences of parental age for offspring fitness and test for age‐assortative mating in a short‐lived bird, the house wren (Troglodytes aedon). Offspring immunoresponsiveness increased with maternal age and decreased with paternal age, but the strength of these effects varied with the age of one's mate. Offspring immunoresponsiveness was augmented most with older mothers and younger fathers. Thus, we expected this combination of ages to yield the highest offspring fitness. However, offspring recruitment, longevity, and lifetime reproductive success were greatest when both parents were of above‐average age. Consistent with the interactive effects of parental age on offspring fitness, we detected positive age‐assortative mating among breeding pairs. Our results suggest that selection favors age‐assortative mating, but in different ways depending on how parental ages affect offspring. We suggest that, in this short‐lived species, selection for combinations of parental ages that maximize offspring immune responses is likely weaker than selection to produce breeding adults.
Corticosterone transdermal application in toads (Rhinella icterica): Effects on cellular and humoral immunity and steroid plasma levels
Authors: Assis Vania Regina , Monteiro Titon Stefanny Christie , Teixeira Queiroz‐Hazarbassanov Nicolle Gilda , de Oliveira Massoco Cristina , Ribeiro Gomes Fernando
Published: August 2017

Previous studies in a variety of vertebrates show stressed animals to exhibit acute increases in glucocorticoid levels, with consequences for immune modulation. Chronically elevated glucocorticoid levels are mostly associated with immunosuppression. However, there is still a paucity of knowledge regarding the amphibian physiological reaction to short‐ and long‐term stress conditions, including glucocorticoid effects on the immune response. In order to better clarify the relationship between glucocorticoids and immune response, newly captured Brazilian toads (Rhinella icterica) (1 week in captivity) were subjected to a daily transdermal application (TA), of corticosterone or vehicle, for 30 consecutive days. Measures were made on the first day (acute stressor) and last day (chronic stressor), at timepoints 1, 6, and 12 hr post TA. A number of variables were analyzed: corticosterone plasma levels (CORT); neutrophil/lymphocyte ratio (N:L); testosterone plasma levels (T); innate immune response, as indicated by bacterial killing ability (BKA); and whole blood phagocytosis. The corticosterone TA only simulated hormonal changes associated with the acute stress response, even after 30 consecutive days of the treatment, with the increased CORT in response after corticosterone TA being evident only 1 hr postapplication and not thereafter. The general responses to corticosterone TA included increased CORT and N:L at first day of the treatment, and increased CORT and phagocytosis on the last day of the treatment. A decrease in T and BKA associated with the time in captivity was also evident, suggesting that captivity may be a chronic stressor for these toads.
Maternal inheritance of Nanog ortholog in blunt‐snout bream
Authors: Yu Miao , Xue Ting , Chen Tiansheng , Fang Jian , Pan Qihua , Deng Yu , Li Lingyu , Chen Kai , Wang Yizhou
Published: August 2017

The homeodomain transcription factor Nanog plays an essential role in maintaining pluripotency and self‐renewal of embryonic stem cells in mammals. However, the evolutionary conservation of its ortholog in teleosts remains elusive. Here we isolated and characterized a Nanog homolog named as Ma‐Nanog in blunt‐snout bream (Megalobrama amblycephala). The full‐length genomic sequence is 3,326 bp in length and consists of four exons encoding a homeodomain protein of 386 amino acid residues. Comparison of protein sequences revealed that Ma‐Nanog is highly homologous to those in other teleosts, particularly in the homeodomain region. During embryogenesis, RNA expression of Nanog was only detected in early developmental embryos, predominantly at the blastula stage, which suggested the transcripts were mainly present in pluripotent stem cells. RNA fluorescence in situ hybridization verified that the signal of the transcripts is present in the germ cells. RNA expression was observed in the oogonia and early stage of oocytes in the ovary, or in the spermatogonia, spermatocytes, and spermatids in the testis. Surprisingly, the transcripts were also detected in adult tissues such as in liver by RT‐PCR or qRT‐PCR. Subcellular localization of the Nanog protein was also verified in nuclei. Taken together, these results suggested that Ma‐Nanog is maternally inherited with conserved features, thus can be potentially used as a marker for stem cells in blunt‐snout bream.
Climatic variability of the Pacific and Atlantic Oceans and western US snowpack
Authors: Pathak Pratik , Kalra Ajay , Lamb Kenneth W. , Miller William P. , Ahmad Sajjad , Amerineni Rajesh , Ponugoti Devi P.
Published: August 2017

This study examines the changing characteristics of snow water equivalent (SWE) in western United States and their teleconnections with large‐scale variability of the Pacific and Atlantic Oceans. This study evaluated the relationship among sea surface temperatures (SST), 500‐mbar geopotential height (Z500), 500‐mbar east–west wind (U500), and western United States SWE (1 March, 1 April, and 1 May). The averages of SST, Z500, and U500 were computed to create a lead time of 2–10 months. Three different 6‐month series were computed – January–June, April–September, and July–December – and were correlated with SWE stations in the western United States. The study utilized singular‐value decomposition (SVD) for a period of 1961–2016 to correlate the SWE and climate indices. SVD was applied between the standardized SST and SWE to obtain their correlation and to evaluate connection with Z500 and U500 within the same SVD relationship. Specifically, SVD was not applied independently on each variable prior to this study. The correlations were observed to increase as the lead time decreased. First mode SVD showed a pronounced non‐El Niño‐Southern Oscillation short‐wave train for the July–December climate in the Z500 data; this terminated over the Great Lakes region, and was strongly correlated with the warming of the SST near the east coast of Japan, resulting in decreased SWE in the study area. Second mode SVD showed a negative correlation between SWE stations in Colorado and Utah and SST near the Asian and Australian continents. The associations between climate indices and SWE that were identified during this study could be used to improve long‐term forecasts, resulting in better management of water resources in the region.
The genetic profile of Leber congenital amaurosis in an Australian cohort
Authors: Thompson Jennifer A. , De Roach John N. , McLaren Terri L. , Montgomery Hannah E. , Hoffmann Ling H. , Campbell Isabella R. , Chen Fred K. , Mackey David A. , Lamey Tina M.
Published: August 2017

Background

Leber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.

Methods

We have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next‐generation sequencing and Array CGH technology.

Results

We present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort.

Conclusion

The high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non‐hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first‐tier test for LCA.
Compound heterozygous CASQ2 mutations and long‐term course of catecholaminergic polymorphic ventricular tachycardia
Authors: Josephs Katherine , Patel Kunjan , Janson Christopher M. , Montagna Cristina , McDonald Thomas V.
Published: August 2017

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac disorder characterized by episodic ventricular tachycardia during adrenergic stimulation. It is associated with significant morbidity and mortality. Knowledge of the underlying genetic cause, pathogenesis, and the natural history of the disease remains incomplete. Approximately 50% of CPVT cases are caused by dominant mutations in the cardiac ryanodine receptor (RYR2) gene, <5% of cases are accounted for by recessive mutations in cardiac calsequestrin (CASQ2) or Triadin (TRDN).

Methods

We report a family with two CASQ2 gene mutations. A research‐based next‐generation sequencing (NGS) initiative was used in a patient with a severe CPVT phenotype and her clinically unaffected son. Reverse transcription polymerase chain reaction (RT‐PCR) from platelet RNA was used to assess the consequences of predicted splice variants.

Results

NGS revealed that the proband carried a novel c.199C>T (p.Gln67*) mutation and a previously reported splice site mutation c.532+1G>A in CASQ2. Her son is a heterozygous carrier of the c.199C>T (p.Gln67*) mutation alone and the proband was compound heterozygous at CASQ2. RNA analysis demonstrated that the splice site mutation results in the retention of intron 3 with no full‐length CASQ2 mRNA.

Conclusion

This study describes a novel CPVT genotype and further characterizes the effect of a previously reported CASQ2 splice site mutation. The long‐term follow‐up of 23 years since first symptom provides additional insight into the natural history of CASQ2‐associated CPVT.
A Lagrangian gradient smoothing method for solid‐flow problems using simplicial mesh
Authors: Mao Zirui , Liu G. R.
Published: August 2017

A novel Lagrangian gradient smoothing method (L‐GSM) is developed to solve “solid‐flow” (flow media with material strength) problems governed by Lagrangian form of Navier‐Stokes equations. It is a particle‐like method, similar to the smoothed particle hydrodynamics (SPH) method but without the so‐called tensile instability that exists in the SPH since its birth. The L‐GSM uses gradient smoothing technique to approximate the gradient of the field variables, based on the standard GSM that was found working well with Euler grids for general fluids. The Delaunay triangulation algorithm is adopted to update the connectivity of the particles, so that supporting neighboring particles can be determined for accurate gradient approximations. Special techniques are also devised for treatments of 3 types of boundaries: no‐slip solid boundary, free‐surface boundary, and periodical boundary. An advanced GSM operation for better consistency condition is then developed. Tensile stability condition of L‐GSM is investigated through the von Neumann stability analysis as well as numerical tests. The proposed L‐GSM is validated by using benchmarking examples of incompressible flows, including the Couette flow, Poiseuille flow, and 2D shear‐driven cavity. It is then applied to solve a practical problem of solid flows: the natural failure process of soil and the resultant soil flows. The numerical results are compared with theoretical solutions, experimental data, and other numerical results by SPH and FDM to evaluate further L‐GSM performance. It shows that the L‐GSM scheme can give a very accurate result for all these examples. Both the theoretical analysis and the numerical testing results demonstrate that the proposed L‐GSM approach restores first‐order accuracy unconditionally and does not suffer from the tensile instability. It is also shown that the L‐GSM is much more computational efficient compared with SPH, especially when a large number of particles are employed in simulation.
Pharmacoepidemiology of testosterone: Curbing off‐label prescribing
Authors: Handelsman David J.
Published: August 2017

Objectives

To estimate the impact of the first year of new Pharmaceutical Benefits Scheme (PBS) prescribing criteria that dictate eligibility for national health scheme subsidy of testosterone prescribing.

Design

Analysis of cumulative PBS data.

Setting

Retrospective analysis of testosterone prescribing from PBS data.

Participants

Nil

Main outcome measures

PBS expenditure analysed by total expenditure, by state, and by product type as well as the age, indication, and prescriber type for new testosterone treatment.

Results

Total PBS expenditure continued to exceed $20 million in 2014 before declining from 2015 with changes that were uniform by state and product type. Prior to 2015, over 80% were for men aged over 40 years of age for low circulating testosterone in the absence of reproductive system disorders (“Low T”) initiated by GPs. From 2015, these features were markedly reduced without changing the numbers of new prescriptions for pathological reproductive disorders or specialist initiations.

Conclusions

The short‐term impact of 2015 PBS criteria showed highly effective and well‐targeted curbing of off‐label testosterone prescribing. The findings indicate that the main driver for the recent upsurge in testosterone prescribing was treatment of middle‐aged men for “Low T” initiated by GPs.
Why do oncologists hide the truth? Disclosure of cancer diagnoses to patients in China: A multisource assessment using mixed methods
Authors: Gan Yiqun , Zheng Lei , Yu Nancy Xiaonan , Zhou Guangyu , Miao Miao , Lu Qian
Published: August 2017

Objective

In the United States and most European countries, cancer diagnoses are disclosed to patients. In China, however, the trend toward full disclosure has progressed slowly. The present study aimed to explore attitudes toward truth‐telling practice among physicians, patients, patients' family members, and the general population, and reasons for nondisclosure.

Methods

We administered a short survey to 212 physicians, 143 patients with cancer, 413 family members of patients with cancer, and 1415 members of the general population. A MANOVA was performed to examine group differences in attitudes toward cancer disclosure. In addition, we interviewed 20 oncologists. Interview data were analyzed using NVivo10. After the interview, we administered another short survey to 143 patients with cancer.

Results

Quantitative data indicated that physicians were the least, and patients the most, in favor of disclosure. Qualitative data among physicians and follow‐up surveys among cancer patients revealed 5 reasons for the concealment of cancer diagnoses by physicians, including lack of awareness of patients' right to knowledge, cultural influences, insufficient medical resources and training, families' financial concerns, and the need to protect doctors from violence.

Conclusion

There is a discrepancy between the needs of patients and those in medical practice. These results deepen our understanding regarding the reasons for oncologists' attitudes toward nondisclosure.
Plasma‐treated polyethylene as electrochemical mediator for enzymatic glucose sensors: Toward bifunctional glucose and dopamine sensors
Authors: Buendía Jorge J. , Fabregat Georgina , Castedo Alejandra , Llorca Jordi , Alemán Carlos
Published: August 2017

The application of inert and insulating low density polyethylene (LDPE) in electrochemical detection is null. However, in a recent study it was found that reactive species formed onto the surface of plasma‐treated LDPE and other polymers promote the electrocatalytic oxidation of dopamine. In this work, we examine the role of plasma‐treated LDPE as mediator in enzymatic glucose biosensors based on Glucose oxidase and glass carbon substrate. Results indicate that plasma‐induced changes facilitate the electrocommunication between the enzyme and the substrate. The chronoamperometric response of these sensors prove their bifunctionality since the oxidation of glucose to gluconolactone, which is catalyzed by the GOx, coexists with the oxidation of dopamine that is electrocatalytized by the plasma activated LDPE surface.
Gene flow from single and stacked herbicide‐resistant rice (Oryza sativa): modeling occurrence of multiple herbicide‐resistant weedy rice
Authors: Dauer Joseph , Hulting Andrew , Carlson Dale , Mankin Luke , Harden John , Mallory‐Smith Carol
Published: August 2017

BACKGROUND

Provisia™ rice (PV), a non‐genetically engineered (GE) quizalofop‐resistant rice, will provide growers with an additional option for weed management to use in conjunction with Clearfield® rice (CL) production. Modeling compared the impact of stacking resistance traits versus single traits in rice on introgression of the resistance trait to weedy rice (also called red rice). Common weed management practices were applied to 2‐, 3‐ and 4‐year crop rotations, and resistant and multiple‐resistant weedy rice seeds, seedlings and mature plants were tracked for 15 years.

RESULTS

Two‐year crop rotations resulted in resistant weedy rice after 2 years with abundant populations (exceeding 0.4 weedy rice plants m–2) occurring after 7 years. When stacked trait rice was rotated with soybeans in a 3‐year rotation and with soybeans and CL in a 4‐year rotation, multiple‐resistance occurred after 2–5 years with abundant populations present in 4–9 years. When CL rice, PV rice, and soybeans were used in 3‐ and 4‐year rotations, the median time of first appearance of multiple‐resistance was 7–11 years and reached abundant levels in 10–15 years.

CONCLUSION

Maintaining separate CL and PV rice systems, in rotation with other crops and herbicides, minimized the evolution of multiple herbicide‐resistant weedy rice through gene flow compared to stacking herbicide resistance traits. © 2017 Society of Chemical Industry
Characteristic Luminescence Correlated with Leaky Diamond Schottky Barrier Diodes
Authors: Shimaoka Takehiro , Teraji Tokuyuki , Watanabe Kenji , Koizumi Satoshi
Published: August 2017

This paper reports correlation between reverse current (IR) of diamond Schottky barrier diodes (SBDs) and luminescence feature. p‐Type vertical SBDs were characterized by current–voltage and cathodoluminescence (CL) measurements. From an exciton image taken at the electrode deposited area, non‐luminescence spots with number density of 104–105 cm−2 were confirmed. No marked relation was found between the density of non‐luminescence spots and IR. A larger IR of >10−5 A was observed when an electrode was deposited on an area that showed bright Band‐A luminescence spots in the CL image. In addition, diodes on the belt‐shaped luminescence in the Green‐band image showed large IR.
A multi-stage genome-wide association study of uterine fibroids in African Americans
Authors: Hellwege Jacklyn N. , Jeff Janina M. , Wise Lauren A. , Gallagher C. Scott , Wellons Melissa , Hartmann Katherine E. , Jones Sarah F. , Torstenson Eric S. , Dickinson Scott , Ruiz-Narváez Edward A. , Rohland Nadin , Allen Alexander , Reich David , Tandon Arti , Pasaniuc Bogdan , Mancuso Nicholas , Im Hae Kyung , Hinds David A. , Palmer Julie R. , Rosenberg Lynn , Denny Joshua C. , Roden Dan M. , Stewart Elizabeth A. , Morton Cynthia C. , Kenny Eimear E. , Edwards Todd L. , Velez Edwards Digna R.
Published: August 2017

Uterine fibroids are benign tumors of the uterus affecting up to 77% of women by menopause. They are the leading indication for hysterectomy, and account for $34 billion annually in the United States. Race/ethnicity and age are the strongest known risk factors. African American (AA) women have higher prevalence, earlier onset, and larger and more numerous fibroids than European American women. We conducted a multi-stage genome-wide association study (GWAS) of fibroid risk among AA women followed by in silico genetically predicted gene expression profiling of top hits. In Stage 1, cases and controls were confirmed by pelvic imaging, genotyped and imputed to 1000 Genomes. Stage 2 used self-reported fibroid and GWAS data from 23andMe, Inc. and the Black Women’s Health Study. Associations with fibroid risk were modeled using logistic regression adjusted for principal components, followed by meta-analysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency = 0.27) in CYTH4 (OR (95% confidence interval) = 1.23 (1.16–1.30), p value = 7.82 × 10−9). Evaluation of the genetic association results with MetaXcan identified lower predicted gene expression of CYTH4 in thyroid tissue as significantly associated with fibroid risk (p value = 5.86 × 10−8). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids within CYTH4 that impacts gene expression in thyroid and has potential biological relevance for fibroids.
Predictability and inconsistencies in the cognitive outcome of early treated PKU patients
Authors: Manti Filippo , Nardecchia Francesca , Paci Sabrina , Chiarotti Flavia , Carducci Claudia , Carducci Carla , Dalmazzone Silvia , Cefalo Graziella , Salvatici Elisabetta , Banderali Giuseppe , Leuzzi Vincenzo
Published: August 2017

Long‐term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra‐ and interindividual variability in the developmental trajectory which cannot be predicted by the disease's biomarkers. We collected biochemical data from 65 ETPKU patients (diagnostic blood Phe > 360 μmol/l) who were assessed twice for IQ (Wechsler Intelligence Scale) during their lifetime (mean age: 10.2 and 19.6 years, respectively). Results show that in ETPKU patients IQ over the second decade of life remained stable in about half of the patients (51%); while the rest experienced a gain (7 to 15 points) or loss (7 to 28 points) in IQ scores (23 and 26% respectively) whatever the quality of metabolic control was. The main factor affecting the second IQ was the value of the first IQ (p < 0.000) whose effect overruled that of the markers of metabolic control. Looking at the developmental trajectory of our ETPKU patients, the present study disclosed a remarkable interindividual variability in their cognitive outcome and also an inconsistent linkage between cognitive performances and biochemical control, thus supporting the hypothesis of an individual resilience or vulnerability to Phe in young adult ETPKU.
The UMP Exact Test and the Confidence Interval for Person Parameters in IRT Models
Authors: Liu Xiang , Han Zhuangzhuang , Johnson Matthew S.
Published: August 2017

In educational and psychological measurement when short test forms are used, the asymptotic normality of the maximum likelihood estimator of the person parameter of item response models does not hold. As a result, hypothesis tests or confidence intervals of the person parameter based on the normal distribution are likely to be problematic. Inferences based on the exact distribution, on the other hand, do not suffer from this limitation. However, the computation involved for the exact distribution approach is often prohibitively expensive. In this paper, we propose a general framework for constructing hypothesis tests and confidence intervals for IRT models within the exponential family based on exact distribution. In addition, an efficient branch and bound algorithm for calculating the exact p value is introduced. The type-I error rate and statistical power of the proposed exact test as well as the coverage rate and the lengths of the associated confidence interval are examined through a simulation. We also demonstrate its practical use by analyzing three real data sets.
Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance
Authors: Davis Amanda N. , Clegg J. L. , Perry C. A. , McFadden J. W.
Published: August 2017

The progression of insulin resistance in dairy cows represents a maternal adaptation to support milk production during heightened energy demand; however, excessive adipose tissue lipolysis can develop. In diabetic non‐ruminants, the mechanisms that mediate insulin resistance involve the sphingolipid ceramide. We tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. Nine dairy cows were utilized in a replicated 3 × 3 Latin square design. Cows were ad libitum fed, nutrient‐restricted (NR), or NR with nicotinic acid (NA; 5 mg of NA/h per kg BW; delivered i.v.) for 34 h. When provided access, cows were ad libitum fed a mixed ration of grass hay and ground corn to meet requirements. Intake for NR cows was limited to vitamins and minerals. Nicotinic acid was administered to suppress lipolysis. Saline was infused in cows not provided NA. At 32 and 33 h of treatment, a liver biopsy and insulin tolerance test were performed, respectively. Samples were analyzed using colorimetry, immunoassay, and mass spectrometry. Nutrient restriction increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, NA infusion was unable to prevent these responses. We also show that NR increases hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0‐Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In conclusion, our results suggest that ceramide accrual represents a metabolic adaptation to nutrient restriction and impaired insulin action in dairy cows.
Widening the net: exploring social determinants of burden of informal carers
Authors: Gresswell I. , Lally L. , Adamis D. , McCarthy G. M.
Published: August 2017

Objectives

Providing care for a person with dementia or other chronic illness at home often places stress on the primary caregiver. In an Irish population, ~67% of carers reported experiencing extreme physical or mental tiredness. This study aimed to identify factors that influence carer burden and identify the sub-populations of carers who are most susceptible to burden.

Methods

Consecutive carers referred to a local carers’ support organisation completed the following measurements: the Neuropsychiatric Inventory, Zarit Burden Interview, Social Network Index, General Health Questionnaire, Short Form Survey, Hamilton Depression Rating Scale, Brown’s Locus of Control scale and provided demographic data on themselves and their patient.

Results

The sample consisted 53 carers, mean age: 64.5±11.7, of whom 43 (81.1%) were females. A linear regression model found significant independent (p<0.05) factors for carer burden were: increased behavioural problems of the patient, carer characteristics including female gender, younger age, high number of contacts, lower physical functioning and emotional problems, while protective factors were marriage and higher number of embedded networks.

Conclusions

The ability to predict which carers are more susceptible to burden allows service providers to more quickly and accurately identify ‘higher risk’ carers, facilitating routine check-ups by physicians and carer support services.
Post-glacial Foraminifera of the incised Yangtze paleo-valley and paleoenvironmental implications
Authors: Ke Xue , Li Baohua , Zhang Zongyan , Wei Yi , Hu Fei , Fan Dongwen , Sun Li , Xie Jianlei , Yu Junjie , Yao Huazhou
Published: August 2017

Three gravity cores (LZK1, ZKA4, and CSJA6) from the incised Yangtze paleo-valley comprise a thick sequence of the post-glacial deposit. Nineteen genera (26 species) of the benthic foraminifers are described from these cores, with detailed down-core foraminiferal variations to investigate their paleoenvironmental implications. Three foraminiferal assemblages are recognized for the lower, middle, and upper parts of the cores respectively. The lower part is dominated byAmmonia beccariivar. andFlorilus decoruswith lower abundance and diversity. In the middle part, the foraminifers are abundant and diverse, dominated by bothAmmonia beccariivar. andElphidium advenum.Cavarotalia annectens,Pararotalia nipponica, and porcellaneous benthic foraminiferal forms are always present, sometimes abundant. The upper part is characterized by theAmmonia beccarii-Elphidium magellanicumassemblage, except for the Core ZKA4, which is barren of foraminifers in this interval. AMS14C dates and foraminiferal assemblages both confirm that the transgression-regression sequence in these cores belongs to the “Ammoniatransgression” during the Holocene. In addition to documenting the post-glacial sea-level fluctuations, the benthic foraminifers also reflect a warmer climate during the early–middle Holocene. The foraminiferal differences among the three cores can be used to interpret the influence of seawater during the post-glacial sea-level fluctuations. The area in the vicinity of Core ZKA4 was affected by marine water only during the middle Holocene, which was much shorter than the areas of the other cores.
General Self-Efficacy and Psychological Resilience Promote Skill Acquisition Rate Under Psychological Pressure
Authors: Crane Monique F. , Brabazon Gareth , Gucciardi Daniel F. , Loveday Thomas , Wiggins Mark
Published: August 2017

This study extends the limited body of research exploring the association between psychological resources and performance under pressure. It was anticipated that participants’ general self-efficacy and resilience would positively influence skill acquisition rate more under high pressure, than low pressure. Eighty-one undergraduate students (Mage = 22.93; SD = 7.53; 50.6% female) participated in a learning task: to fly a flight simulator. The within-subjects variable was the participant's ability to steadily control the aircraft roll across six trials. Psychological pressure was manipulated between-subjects and general self-efficacy and resilience were measured moderator variables. Findings indicated that under high pressure, higher levels of general self-efficacy and perceived resilience predicted faster initial skill acquisition compared to those with lower levels of these resources. In contrast, in the low-pressure condition, the skill acquisition rate was the same irrespective of psychological resources. This research highlights the importance of psychological resources in pressured training contexts.