bluuebunny/crossref_metadata_2025 huggingface dataset:
Access by Design, Benefits if Convenient: A Closer Look at the Pandemic Influenza Preparedness Framework's Standard Material Transfer Agreements
Authors: ROURKE MICHELLE F.
Published: January 2019

Policy Points

Securing access to pathogen samples for research purposes is crucial for pandemic preparedness and responding to infectious disease outbreaks.

The Pandemic Influenza Preparedness Framework (PIP Framework) is the only pathogen‐specific international access and benefit‐sharing (ABS) instrument.

This analysis reveals that during an influenza pandemic, the PIP Framework will safeguard access to virus samples but may not be as effective in delivering the associated benefits, like vaccines and antivirals, to countries in need.

The PIP Framework's deficiencies must be addressed before an influenza pandemic and before this ABS model is extended to other human pathogens.

Context

The World Health Organization (WHO) adopted the Pandemic Influenza Preparedness Framework (PIP Framework) after being forced to grapple with the demands of developing countries for the fairer distribution of vaccines and antivirals created using influenza viruses isolated from within their territories. Though adopted as a nonbinding resolution, the PIP Framework has been praised for its novel legal approach to access and benefit‐sharing (ABS), using Standard Material Transfer Agreements (SMTAs) to create binding terms and conditions on both providers and users of PIP biological materials. The PIP Framework's SMTA1 regulates the movement of influenza viruses with human pandemic potential through the WHO's Global Influenza Surveillance and Response System (GISRS) as it operates to monitor the spread of seasonal influenza and detect the emergence of pandemic strains. Member States give consent to the WHO to transfer their materials to third parties under the terms of a negotiated SMTA2. The SMTA2 details benefits such as vaccines and antivirals to be made available to the WHO for distribution in the event of an influenza pandemic.

Methods

I analyzed the PIP Framework, its SMTAs, and secondary sources to determine whether the PIP Framework will effectively function as an ABS instrument during an influenza pandemic.

Findings

The SMTAs do not create any direct or binding agreements between Member States and third‐party recipients of influenza viruses. In the lead‐up to and during a pandemic, the SMTA1 secures access to influenza viruses for the WHO, and the SMTA2 secures access for commercial users of virus samples, but the SMTA2 may be ineffective in securing tangible benefits for the sovereign providers of those materials.

Conclusions

As the international community starts to consider how to best regulate access to nonpandemic influenza pathogen samples, it is imperative that we first address the shortcomings of the only pathogen‐specific international ABS instrument available, and we should do so before it is put to the ultimate test.
Genotype‐free estimation of allele frequencies reduces bias and improves demographic inference from RADSeq data
Authors: Warmuth Vera M. , Ellegren Hans
Published: January 2019

Restriction‐site associated DNA sequencing (RADSeq) facilitates rapid generation of thousands of genetic markers at relatively low cost; however, several sources of error specific to RADSeq methods often lead to biased estimates of allele frequencies and thereby to erroneous population genetic inference. Estimating the distribution of sample allele frequencies without calling genotypes was shown to improve population inference from whole genome sequencing data, but the ability of this approach to account for RADSeq‐specific biases remains unexplored. Here we assess in how far genotype‐free methods of allele frequency estimation affect demographic inference from empirical RADSeq data. Using the well‐studied pied flycatcher (Ficedula hypoleuca) as a study system, we compare allele frequency estimation and demographic inference from whole genome sequencing data with that from RADSeq data matched for samples using both genotype‐based and genotype free methods. The demographic history of pied flycatchers as inferred from RADSeq data was highly congruent with that inferred from whole genome resequencing (WGS) data when allele frequencies were estimated directly from the read data. In contrast, when allele frequencies were derived from called genotypes, RADSeq‐based estimates of most model parameters fell outside the 95% confidence interval of estimates derived from WGS data. Notably, more stringent filtering of the genotype calls tended to increase the discrepancy between parameter estimates from WGS and RADSeq data, respectively. The results from this study demonstrate the ability of genotype‐free methods to improve allele frequency spectrum‐ (AFS‐) based demographic inference from empirical RADSeq data and highlight the need to account for uncertainty in NGS data regardless of sequencing method.
Regularized S‐map for inference and forecasting with noisy ecological time series
Authors: Cenci Simone , Sugihara George , Saavedra Serguei
Published: January 2019

It is well known that fluctuations of species abundances observed in ecological time series emerge from an interplay between deterministic nonlinear dynamics and stochastic forces. Importantly, nonlinearity and stochasticity introduce significant challenges to the analysis of ecological time series, such as the inference of the effect of species interactions on community dynamics and forecasting of species abundances.

Local linear fits with state‐space‐dependent kernel functions, known as S‐maps, provide an efficient method to infer Jacobian coefficients (a proxy for the local effect of species interactions) and to make reliable forecasts from nonlinear time series. Yet, while it has been shown that the S‐map outperforms existing methods for nonparametric inference and forecasting, the methodology is sensitive to process noise. To overcome this limitation, we integrate the S‐map with different regularization schemes.

To validate our approach, we test our methodology against different levels of noise and nonlinearity using three standard population dynamics models. We show that an appropriate choice of the regularization scheme, alongside an accurate choice of the kernel functions, can significantly improve the in‐sample inference of Jacobian coefficients and the out‐of‐sample forecast of species abundances in the presence of process noise. We further validate our methodology using two empirical time series of marine microbial communities.

Our results illustrate that the regularized S‐map is an efficient method for nonparametric inference and forecasting from noisy, nonlinear, ecological time series. Yet, attention must be paid on the regularization scheme and the structure of the kernel for whether inference or forecasting is the ultimate goal of a research study.
Exploring synchronous, remote collaborative interaction between learners using multi‐touch tables and video conferencing in UK primary schools
Authors: Beauchamp Gary , Joyce‐Gibbons Andrew , Mc Naughton James , Young Nick , Crick Tom
Published: January 2019

This study explores remote, non‐collocated collaboration via multi‐touch table (SynergyNet) and video conferencing software (Skype). Twenty‐four participants (aged 10‐11 years) in two locations—primary school classrooms located 300 miles apart in the UK—engaged in simultaneous collaborative activity to solve a History mystery task. Audio‐video data recorded in the first minute of the activity were analysed to explore the emergence of collaborative working practices both within groups in the same location (resizing for shared reading) and between the groups communicating via video conferencing software and through the “flick” multi‐touch gesture (sharing clues between groups). The results indicated that most groups focused first on the establishment of intra‐group collaboration before reaching out to their remotely located partners. However, when the second data set was analysed, audio data from delayed interviews conducted after the original study, participants reported that the discussion between groups supported by the “flick” gesture was the most important and memorable feature of the activity. The study relates these findings to the existing literature on collaborative learning using multi‐touch tables and considers how teachers are best able to help support the emergence of collaborative practices.
Salvation of the fallen angel: Reactivating mutant p53
Authors: Li Yang , Wang Zhuoyi , Chen Yuchen , Petersen Robert B. , Zheng Ling , Huang Kun
Published: January 2019

The transcription factor p53 is known as the guardian of the genome for its powerful anti‐tumour capacity. However, mutations of p53 that undermine their protein structure, resulting in loss of tumour suppressor function and gain of oncogenic function, have been implicated in more than half of human cancers. The crucial role of mutant forms of p53 in cancer makes it an attractive therapeutic target. A large number of candidates, including low MW compounds, peptides, and nucleic acids, have been identified or designed to rescue p53 mutants and reactivate their anti‐tumour capacity through a variety of mechanisms. In this review, we summarize the progress made in the reactivation of mutant forms of p53, focusing on the pharmacological mechanisms of the reactivators of p53 mutants.
Pterostilbene prevents hepatocyte epithelial‐mesenchymal transition in fructose‐induced liver fibrosis through suppressing miR‐34a/Sirt1/p53 and TGF‐β1/Smads signalling
Authors: Song Lin , Chen Tian‐Yu , Zhao Xiao‐Juan , Xu Qiang , Jiao Rui‐Qing , Li Jian‐Mei , Kong Ling‐Dong
Published: January 2019

Background and Purpose

Excessive fructose consumption is a risk factor for liver fibrosis. Pterostilbene protects against liver fibrosis. Here, we investigated the potential role and the mechanisms underlying the hepatocyte epithelial‐mesenchymal transition (EMT) in fructose‐induced liver fibrosis and protection by pterostilbene.

Experimental Approach

Characteristic features of liver fibrosis in 10% fructose‐fed rats and EMT in 5 mM fructose‐exposed BRL‐3A cells with or without pterostilbene and the change of miR‐34a/Sirt1/p53 and transforming growth factor‐β1 (TGF‐β1)/Smadssignalling were examined. MiR‐34a inhibitor, miR‐34a minic, orp53siRNA were used to explore the role of miR‐34a/Sirt1/p53 signalling in fructose‐induced EMT and the action of pterostilbene.

Key Results

Pterostilbene prevented fructose‐induced liver injury with fibrosis in rats. Fructose caused hepatocyte undergoing EMT, gaining fibroblast‐specific protein 1 and vimentin, and losing E‐cadherin, effects attenuated by pterostilbene. Moreover, fructose induced miR‐34a overexpression in hepatocytes with down‐regulated Sirt1, increased p53 and ac‐p53, and activated TGF‐β1/Smads signalling, whereas these disturbances were suppressed by miR‐34a inhibitor. Additionally, miR‐34a inhibitor andp53siRNA prevented TGF‐β1‐driven hepatocyte EMT under fructose exposure. Pterostilbene down‐regulated miR‐34a, up‐regulated Sirt1, and suppressed p53 activation and TGF‐β1/Smads signalling in fructose‐stimulated animals and cells but showed no additional effects with miR‐34a inhibitor on miR‐34a/Sirt1/p53 signalling in fructose‐exposed hepatocytes.

Conclusions and Implications

These results strongly suggest that activation of miR‐34a/Sirt1/p53 signalling is required for fructose‐induced hepatocyte EMT mediated by TGF‐β1/Smads signalling, contributing to liver fibrosis in rats. Pterostilbene exhibits a protective effect against liver fibrosis at least partly through inhibiting miR‐34a/Sirt1/p53 signalling activation.
Anti‐cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate
Authors: Guo Ziyang , Pei Hailong , Nie Jing , Hu Wentao , Zhang Jian , Ding Jiahan , Pan Shuxian , Li Bingyan , Hei Tom K. , Chen Weiqiang , Zhou Guangming
Published: January 2019

Aim

Autophagy is a self‐protective process, and it confers cancer cells resistance against radio‐chemotherapeutics. To induce cancer cell death, a series of compounds of 3‐((4‐((7‐chloroquinolin‐4‐yl)amino)butyl)amino)‐7‐substituted benzo[e][1,2,4]triazine 1‐oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1‐oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.

Methods

In vitro cultured non‐small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B‐blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy.

Results

Compared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO‐3 was the most effective. The LD50 for CQBTO‐3 was 21 μΜ in A549 cells and 21.5 μΜ in Calu‐1 cells, which was lower than that of CQBTO‐2 or CQBTO‐1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO‐3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO‐3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.

Conclusion

CQBTO‐3 is a potential chemical compound for lung cancer treatment.
Precalcaneal congenital fibrolipomatous hamartoma: Rare or under‐reported?
Authors: Jakhar Deepak , Kaur Ishmeet , Singal Archana , Sharma Sonal
Published: January 2019

Precalcaneal congenital fibrolipomatous hamartoma (PCFH) is a benign under‐reported condition of infancy characterized by the presence of soft nodules on precalcaneal plantar surface of the heel. These lesions are usually bilateral solitary and asymptomatic. We present a 2‐month‐old infant with solitary skin‐colored nodules present on precalcaneal plantar aspect of bilateral heels.
Epigenetic regulation of myelination in health and disease
Authors: Lu Guozhen , Zhang Ming , Wang Jian , Zhang Kaixiang , Wu Shengxi , Zhao Xianghui
Published: January 2019

Myelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.
C‐reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level
Authors: Yan Siyu , Chen Wangqing , Peng Cong , Zhu Wu , Chen Mingliang , Zhang Jianglin , Su Juan , Li Fangfang , Liu Zhaoqian , Zhang Wei , Li Qingling , Li Jie , Chen Xiang
Published: January 2019

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non‐sedating H1 antihistamine treatment. CRP gene encodes the C‐reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4‐week non‐sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non‐effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and β‐hexosaminidase assay were conducted in HEK293T cells or RBL‐2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR = 4.20, P = 0.015), had lower serum CRP, IL‐6 and TNF‐α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P < 0.001). From the β‐hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL‐2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.
High abundance of an invasive species gives it an outsized ecological role
Authors: McDowell William G. , Byers James E.
Published: January 2019

Many communities are shifting composition, with losses of native species and increases of non‐indigenous species (NIS). At its extreme, such alteration of ecological guilds can result in simplification with a single NIS performing an ecological role once carried out by a suite of natives. This alteration has occurred in many rivers of the south‐eastern U.S.A., where the invasive filter‐feeding freshwater clam Corbicula fluminea has proliferated following the nearly complete extirpation of native mussels.

We investigated the factors controlling the distribution and abundance of Corbicula, as well as estimated the ecological service it provides via water filtration. With a nested design, we surveyed multiple transects within four to six sites within each of four rivers that spanned three large catchments in the Georgia piedmont, collecting data on Corbicula density and physical habitat characteristics associated with its presence.

We found Corbicula present in over half of the 1,536 sampled 0.044 m2 sampled plots, 90 of the 93 transects that spanned the width of the river, and all 1–2 km sample sites, underscoring the clam's ubiquity in the study region. At the river scale, Corbicula densities ranged from 50–212 Corbicula m−2, although individual sites ranged from 7–483 Corbicula m−2. Corbicula was more abundant in areas with higher proportions of gravel, and less abundant with higher proportions of bedrock. A hierarchical model with river, site, and these two substrate variables explained 32% of the variation in Corbicula density.

Using observed densities and published per capita feeding rates, we calculated system‐wide collective filtration rates provided by Corbicula. In the four rivers surveyed and based on estimated residence times for median flows for the summer of 2012, Corbicula is estimated to filter water as many as seven times during median flows and 18 times during minimum flows before water flows out of a 10‐km reach. Due to high abundances and per biomass filtration rates, Corbicula plays an important role in these rivers.

Invasive species, biotic homogenisation, and the loss of functional redundancy may mean that many more rivers are similar to our studied rivers, with a single, often invasive, species dominating ecosystem function. Understanding the influence of biotic homogenisation on ecosystem function is of foremost importance to evaluate the resilience of natural systems.
Competition during early ontogeny: Effects of native and invasive planktivores on the growth, survival, and habitat use of bluegill
Authors: Fletcher Cameron M. , Collins Scott F. , Nannini Michael A. , Wahl David H.
Published: January 2019

Early life stages of fishes are sensitive to ecological and environmental disturbances and experience very high mortality rates. During early ontogeny, the growth and survival of larval fish often depends on food availability. Because habitat and diet shifts are strongly tied to individual body size, factors that influence the growth rates of individuals (e.g. resource limitation, competition) also affect other aspects of ontogeny including the timing of habitat or diet shifts. In the context of biological invasions, non‐native species can potentially disrupt the interaction of larval fish with their food via competition for shared prey, reducing growth and survival during a vulnerable period of an organism's life history.

We hypothesised that invasive planktivores negatively affect native species through the vulnerable larval life stage via competition for zooplankton resources. To test this hypothesis, we conducted a series of experiments to assess and contrast the effects of invasive (bighead carp, Hypophthalmichthys nobilis) and native (golden shiners, Notemigonus crysoleucas) planktivores on zooplankton densities, and their effects on the growth, survival, abundance, and habitat use of larval bluegill (Lepomis macrochirus).

Overall, the effects of the invasive planktivore were consistently greater than the native planktivore in terms of reduced prey densities, reduced bluegill growth rates, and delays to the timing of ontogenetic habitat shifts. Growth rates of bluegill larvae were reduced by 58–87% in the presence of bighead carp and 37% in the presence of golden shiners (relative to controls), but such reductions did not consistently lead to reduced survival (in mesocosm experiment) or relative abundance (in pond experiment). However, we estimated that bighead carp and golden shiners delayed ontogenetic habitat shifts in bluegill by 9–24 and 1–3 days, respectively.

Although we did not detect an effect of planktivores on the numbers of larval bluegill, our findings suggest that bighead carp may still affect bluegill ontogeny and freshwater food webs by disrupting the timing of ontogenetic habitat shifts. By affecting the coupling of habitats via organism movements during early ontogeny, bighead carp may indirectly disrupt predator–prey interactions of native taxa.
Evolution of the latitudinal diversity gradient in the hyperdiverse ant genus Pheidole
Authors: Economo Evan P. , Huang Jen‐Pan , Fischer Georg , Sarnat Eli M. , Narula Nitish , Janda Milan , Guénard Benoit , Longino John T. , Knowles L. Lacey
Published: January 2019

Aim

The latitudinal diversity gradient is the dominant geographic pattern of life on Earth, but a consensus understanding of its origins has remained elusive. The analysis of recently diverged, hyper‐rich invertebrate groups provides an opportunity to investigate latitudinal patterns with the statistical power of large trees while minimizing potentially confounding variation in ecology and history. Here, we synthesize global phylogenetic and macroecological data on a hyperdiverse (> 1,100 species) ant radiation, Pheidole and test predictions of three general explanations for the latitudinal gradient: variation in diversification rates, tropical conservatism and ecological regulation.

Location

Global.

Time period

The past 35 million years.

Major taxa studied

The hyperdiverse ant genus Pheidole Westwood.

Methods

We assembled geographic data for 1,499 species and morphospecies, and inferred a dated phylogeny for 449 species of Pheidole, including 167 species newly sequenced for this study. We tested for correlations between diversification rate and latitude with Bayesian analysis of macroevolutionary mixtures (BAMM), hidden state speciation and extinction (HiSSE), geographic state speciation and extinction (GeoSSE), and a non‐parametric method (FiSSE), evaluated evidence for richness steady state, and examined patterns of diversification as Pheidole spread around the globe.

Results

There was no evidence of systematic variation of net diversification rates with latitude across any of the methods. We found that Pheidole diversification occurred in bursts when new continents were colonized, followed by a slowdown in each region, but there is no evidence richness has saturated at an equilibrium in any region. Additionally, we found latitudinal affinity is moderately conserved with a Neotropical ancestor and simulations show that phylogenetic inertia alone is sufficient to produce the gradient pattern.

Main conclusions

Our results provide no evidence that diversification rates vary systematically with latitude. Richness is far from steady state in each region, contrary to the ecological regulation hypothesis, although there is evidence that ecological opportunity promotes diversification after colonization of new areas. The fact that niche conservatism is strong enough to produce the gradient pattern is in accord with the tropical conservatism hypothesis. Overall, these results shed light on the mechanisms underlying the emergence of the diversity gradient within the past 34 million years, complementing recent work on deeper time‐scales, and more generally contribute toward much‐needed invertebrate perspective on global biodiversity dynamics.
A Cross‐linguistic Examination of Toddlers’ Interpretation of Vowel Duration
Authors: Swingley Daniel , van der Feest Suzanne V. H.
Published: January 2019

Languages differ in their phonological use of vowel duration. For the child, learning how duration contributes to lexical contrast is complicated because segmental duration is implicated in many different linguistic distinctions. Using a language‐guided looking task, we measured English and Dutch 21‐month‐olds’ recognition of familiar words with normal or manipulated vowel durations. Dutch but not English learners were affected by duration changes, even though distributions of short and long vowels in both languages are similar, and English uses vowel duration as a cue to (for example) consonant coda voicing. Additionally, we found that word recognition in Dutch toddlers was affected by shortening but not lengthening of vowels, matching an asymmetry also found in Dutch adults. Considering the subtlety of the cross‐linguistic difference in the input, and the complexity of duration as a phonetic feature, our results suggest a strong capacity for phonetic analysis in children before their second birthday.
Cardiovascular outcomes in patients with diabetes when initiating blood pressure lowering at baseline SBP between 130 and 140 mm Hg: A meta‐analysis
Authors: Wang Shifei , Djama Nima Moumin , Lai Yanxian , Li Hairui , Liao Wangjun , Liao Yulin , Bin Jianping
Published: January 2019

The efficacy and safety of blood pressure (BP) lowering initiated at baseline systolic BP (SBP) of 130‐140 mm Hg in patients with diabetes remain controversial. The authors aimed to investigate the benefits and harms of BP lowering initiated at these levels for patients with diabetes. Medline and EMBASE were searched from inception to March 10, 2018. The primary outcome was major cardiovascular events. Random‐effects model was used to pool all the estimates. Six trials with 21 574 diabetics were included. In diabetics, initiating BP lowering at baseline SBP of 130 and 140 mm Hg did not reduce the rate of major cardiovascular events (RR, 1.01 [95% CI, 0.93‐1.10]), finding that was consistent in subgroup and sensitivity analyses. Moreover, BP lowering did not reduce the risks of myocardial infarction (RR, 0.99 [95% CI, 0.85‐1.16]), stroke (0.83 [95% CI, 0.54‐1.27]), heart failure (0.91 [95% CI, 0.79‐1.04]), albuminuria (0.93 [95% CI, 0.84‐1.04]), end‐stage renal disease (0.93 [95% CI, 0.70‐1.24]), cardiovascular death (1.25 [95% CI, 0.90‐1.74]) and all‐cause death (1.05 [95% CI, 0.94‐1.17]) in patients with diabetes and baseline SBP of 130‐140 mm Hg but possibly increase the risks of serious adverse events (RR, 2.00 [95% CI, 1.33‐3.01]) and hypotension (5.30 [95% CI, 0.99‐28.40]). In diabetics, initiating BP lowering at baseline SBP of 130‐140 mm Hg may not produce any benefit but probably increase the risks of serious adverse events and hypotension. It may not be recommended to initiate BP lowering at a threshold of SBP lower than 140 mm Hg for diabetics.
Circulating serum vitamin D levels and total body bone mineral density: A Mendelian randomization study
Authors: Sun Jing‐yi , Zhao Ming , Hou Yajun , Zhang Cheng , Oh Jinrok , Sun Zheng , Sun Bao‐liang
Published: January 2019

Until recently, randomized controlled trials have not demonstrated convincing evidence that vitamin D, or vitamin D in combination with calcium supplementation could improve bone mineral density (BMD), osteoporosis and fracture. It remains unclear whether vitamin D levels are causally associated with total body BMD. Here, we performed a Mendelian randomization study to investigate the association of vitamin D levels with total body BMD using a large‐scale vitamin D genome‐wide association study (GWAS) dataset (including 79 366 individuals) and a large‐scale total body BMD GWAS dataset (including 66,628 individuals). We selected three Mendelian randomization methods including inverse‐variance weighted meta‐analysis (IVW), weighted median regression and MR‐Egger regression. All these three methods did not show statistically significant association of genetically increased vitamin D levels with total body BMD. Importantly, our findings are consistent with recent randomized clinical trials and Mendelian randomization study. In summary, we provide genetic evidence that increased vitamin D levels could not improve BMD in the general population. Hence, vitamin D supplementation alone may not be associated with reduced fracture incidence among community‐dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture.
HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa
Authors: Peris K. , Lo Schiavo A. , Fabbrocini G. , Dini V. , Patrizi A. , Fusano M. , Bianchi L. , Guanziroli E. , Guarneri C. , Parodi A. , Bertoldi A. , Musumeci M.L. , Offidani A. , Rongioletti F. , Pistone G. , Malara G. , Potenza C. , Casari A. , Franchi C. , Ardigò M. , Cusano F. , Stingeni L. , Amerio P. , Mancini L.L. , Prignano F. , Deboli T. , Gualberti G. , Saragaglia V. , Bettoli V.
Published: January 2019

Background

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland–bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used.

Objective

The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome.

Methods

A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex‐16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment–General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS‐PGA).

Results

A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex‐16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS‐PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test–retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated.

Conclusion

Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.
Physical characterization and mass modeling of dried Terminalia chebula fruit
Authors: Pathak Sumit Sudhir , Pradhan Rama Chandra , Mishra Sabyasachi
Published: January 2019

The research was inducted to investigate the physical properties and to determine the mass model for Terminalia chebula fruits depending on its dimensional attributes. The investigation revealed that principle dimensions of the whole fruit T. chebula viz. average longitudinal axis (length), intermediate axis (width), and transverse axis (thickness) were 31.076 mm, 17.404 mm, and 16.073 mm, respectively. The thousand fruit mass was found to be 3.890 kg while the fruit has a mass distribution over the range of 1.730–9.794 g. The dimensional properties such as arithmetic mean diameter, equivalent mean diameter, and geometric mean diameter were 21.518 mm, 20.553 mm, and 20.538 mm, respectively. The aspect ratio, sphericity, eccentricity, and fruit part fraction were calculated. The surface area and volume were noted to be 1,302.351 mm2 and 10,054.28 mm3, respectively. The frictional properties such as coefficient of friction and angle of friction were measured. Mass modeling was done by using four different models viz. linear, power, quadratic, and s‐curve relating to the mass and dimensional property of the fruit which will be applicable in machine vision for grading systems. The quadratic and linear models showed the best relations between the mass and dimensional parameters of the fruit.

Practical applications

The fruit of Terminalia chebula is a minor forest produce but has a wide application in the traditional medicines and food industries. The determination of the physiological properties such as dimensional, gravimetric, and frictional properties will help researchers, industrial process designers to design the process handling equipment, postharvest machinery, storage structures, grading, sorting equipment, etc., in the processing and manufacturing industries. The fruits can be separated on the basis of mass rather than its shape and size. The mass modeling of the fruit will be beneficial to segregate the fruits on industrial scale with minimal labor and more accuracy by using the relationship for mass of fruit with its physical properties.
Elections and Capital Flows
Authors: HONIG ADAM
Published: January 2019

This paper investigates the extent to which elections affect capital flows. I find little evidence of political capital flow cycles in advanced economies. In emerging and developing countries, however, presidential elections significantly lower preelection foreign direct investment (FDI) inflows but have no effect on other types of capital flows. Furthermore, I find evidence that these cycles are not caused by economic crises related to elections or preelection manipulation of policy variables. These results suggest that uncertainty about future government policies, which should have greater impact on more irreversible forms of capital flows like FDI, may be an important factor in generating this cycle.
Optimal Structure of Fiscal and Monetary Authorities
Authors: MILLER DAVID S.
Published: January 2019

Why are monetary authorities not elected like fiscal authorities are? Advanced economies pair an elected fiscal authority with an independent monetary authority. Replicating the advanced economies' structure with authorities microfounded by a political economy model shows that this structure is the solution to a constrained mechanism design problem that overcomes time inconsistency and results in the highest possible welfare. Goal and instrument independence, singly and in combination, are insufficient to minimize time inconsistency, though their combination is necessary.
Self‐perceived oral health, normative need, and dental services utilization among dentate adults in the United States: National Health and Nutrition Examination Survey (NHANES) 2011‐2014
Authors: Adunola Folasayo , Garcia Isabel , Iafolla Timothy , Boroumand Shahdokht , Silveira Marushka L. , Adesanya Margo , Dye Bruce A.
Published: January 2019

Objective

This study investigated the role of self‐perceived oral health and normative need on dental services utilization by US adults aged ≥30 years from the 2011‐2014 National Health and Nutrition Examination Survey (NHANES).

Methods

Data on 5,806 dentate adult NHANES participants were analyzed. Key independent variables were self‐perceived oral health and normative need assessed by a dentist. The dependent variable was dental visit within the past 12 months. Select sociodemographic variables were adjusted for in logistic regression models using SAS survey procedures.

Results

Overall, 33.8 percent of adults did not have a dental visit in the past 12 months. About 26.9 percent reported they were unsatisfied with their oral health and 53.4 percent needed to seek care. Individuals unsatisfied with their oral health were less likely to have a dental visit in the past 12 months compared to those who were satisfied with their oral health (57 versus 25 percent). Overall, participants who were unsatisfied with their oral health received a recommendation to seek care. These participants had more normative needs and were less likely to have a dental visit in the past 12 months; however, this relationship varied by race/ethnicity. For Asian‐Americans, there was no association between those unsatisfied with their oral health and dental visits. Also, there was no association across all race/ethnicities between number of teeth present and dental visits.

Conclusion

Both self‐perceived oral health and normative need are associated with dental utilization. Results will contribute to health policy discussions and program development that aim to improve oral health status in the United States.
Soy isoflavone-loaded alginate microspheres in thermosensitive gel base: attempts to improve wound-healing efficacy
Authors: Elmowafy Mohammed , Shalaby Khaled , Salama Ayman , Soliman Ghareb M , Alruwaili Nabil K , Mostafa Ehab M , Mohammed Elshaer F , Moustafa Abd El Ghany A , Zafar Ameeduzzafar
Published: January 2019

Objectives

This study aims to develop thermosensitive gel containing soy isoflavone (antioxidant and anti-inflammatory natural agent) alginate microspheres for enhancement of wound-healing performance.

Methods

Soy isoflavone microspheres were prepared by ionic cross-linking method and optimized using the Box–Behnken optimization design. Formulations were characterized in terms of particle size, encapsulation efficiency and equilibrium swelling degree. The optimized formula was incorporated in Pluronic F127 gel base and examined for in vivo wound-healing efficacy.

Key findings

Results showed mean particle size between 18 and 25 μm, encapsulation efficiency of over 75% and equilibrium swelling degree over 1.9. Thermal analysis indicated interaction between alginate and CaCl2 and embedding of soy isoflavone in microspheres. In vivo wound-healing efficacy showed significant advance in re-epithelization, mature collagen synthesis and proangiogenesis. Immunohistochemical investigation exhibited promising alpha-smooth muscle actin immunopositive cells expression, fibroblast activation and expression of proliferating cell nuclear antigen (proliferation marker) in the epidermis and in the dermis.

Conclusions

The developed formulation would appear to be a promising topical preparation for accelerating healing process.
Mummified Magnoliaceae woods from the upper Oligocene of South China, with biogeography, paleoecology, and wood trait evolution implications
Authors: Huang Lu‐Liang , Jin Jian‐Hua , Quan Cheng , Oskolski Alexei A.
Published: January 2019

In this paper, we describe a new species Magnolia nanningensis sp. nov., based on exceptionally well‐preserved mummified fossil woods from the late Oligocene of the Nanning Basin, Guangxi, South China. The features of these woods indicate a close affinity to the section Michelia of the subgenus Yulania belonging to the genus Magnolia sensu lato (Magnoliaceae). Magnolia nanningensis is the first fossil record of the section Michelia from China, the modern diversity center of this group. These mummified woods provide fossil evidence supporting molecular dating that estimated an Oligocene age for divergence of the tropical evergreen section Michelia and the temperate deciduous section Yulania. Helical thickenings on vessel walls and a high degree of vessel grouping found in these fossil woods could be adaptive to temporary, possibly seasonal, droughts and, as suggested by other woods from the Nanning Basin, could be indicative of a monsoon‐influenced tropical climate in Guangxi during the late Oligocene. Helical thickenings have not been reported in magnoliaceous fossil woods prior to the Oligocene. The appearance of this trait was presumably a response to abrupt climate cooling near the Eocene–Oligocene boundary, followed by increase in climate seasonality. The associated increase of latitudinal zonation might be a possible trigger for divergence between the tropical evergreen sect. Michelia and the temperate deciduous sect. Yulania.
Further characterization of carbonaceous materials in Hayabusa‐returned samples to understand their origin
Authors: Uesugi Masayuki , Ito Motoo , Yabuta Hikaru , Naraoka Hiroshi , Kitajima Fumio , Takano Yoshinori , Mita Hajime , Kebukawa Yoko , Nakato Aiko , Karouji Yuzuru
Published: January 2019

Carbonaceous materials in the sample catcher of the Hayabusa spacecraft were assigned as category 3 particles. We investigated the category 3 particles with a suite of in situ microanalytical methods. Possible contaminants collected from the cleanrooms of the spacecraft assembly and extraterrestrial sample curation center (ESCuC) were also analyzed in the same manner as category 3 particles for comparison. Our data were integrated with those of the preliminary examination team for category 3 particles. Possible origins for the category 3 particles include contamination before and after the operation of the Hayabusa spacecraft.
Association mapping of ectomycorrhizal traits in loblolly pine (Pinus taedaL.)
Authors: Piculell Bridget J. , José Martínez‐García Pedro , Nelson C. Dana , Hoeksema Jason D.
Published: January 2019

To understand how diverse mutualisms coevolve and how species adapt to complex environments, a description of the underlying genetic basis of the traits involved must be provided. For example, in diverse coevolving mutualisms, such as the interaction of host plants with a suite of symbiotic mycorrhizal fungi, a key question is whether host plants can coevolve independently with multiple species of symbionts, which depends on whether those interactions are governed independently by separate genes or pleiotropically by shared genes. To provide insight into this question, we employed an association mapping approach in a clonally replicated field experiment of loblolly pine (Pinus taedaL.) to identify genetic components of host traits governing ectomycorrhizal (EM) symbioses (mycorrhizal traits). The relative abundances of different EM fungi as well as the total number of root tips per cm root colonized by EM fungi were analyzed as separate mycorrhizal traits of loblolly pine. Single‐nucleotide polymorphisms (SNPs) within candidate genes of loblolly pine were associated with loblolly pine mycorrhizal traits, mapped to the loblolly pine genome, and their putative protein function obtained when available. The results support the hypothesis that ectomycorrhiza formation is governed by host genes of large effect that apparently have independent influences on host interactions with different symbiont species.
‘Participatory consociationalism? No, but South Tyrol's Autonomy Convention is evidence that power‐sharing can transform conflicts’
Authors: Larin Stephen J. , Röggla Marc
Published: January 2019

South Tyrol is an autonomous, predominantly German‐speaking province in Italy, and one of the most successful cases of power‐sharing in the world. Nevertheless, the Province recently conducted a participatory‐democratic process known as the ‘Autonomy Convention’ to debate and draft a proposal for revising the 1972 Autonomy Statute. It is the first such process with the stated intent of amending a power‐sharing arrangement, and our research questions are whether this represents a new type of consociational negotiation, and what made it possible. The answer to the first question is ‘no’, and the Convention is best seen as a ‘participatory‐ish consultation’ which had no formal power. But the problems that it faced, and the fact that it occurred at all, are evidence of consociational democracy's potential to transform conflicts. The Convention, we argue, is the result of ‘normal’, not ‘ethnic’ politics, and two generations of successful power‐sharing made that possible by desecuritising the relationship between South Tyrol's three official linguistic groups.
Functional anal canal length measurement using high‐resolution anorectal manometry to investigate anal sphincter dysfunction in patients with fecal incontinence or constipation
Authors: Vollebregt Paul F. , Rasijeff Annika M. P. , Pares David , Grossi Ugo , Carrington Emma V. , Knowles Charles H. , Scott S. Mark
Published: January 2019

Background

Using high‐resolution anorectal manometry, we aimed to evaluate the: (a) optimal threshold to measure functional anal canal length (FACL) with intra‐ and inter‐observer variability; (b) relationship between abnormal FACL and other phenotypic findings; and (c) utility of FACL measurement to discriminate between healthy volunteers (HV) and patients with fecal incontinence (FI) or chronic constipation (CC).

Methods

Consecutive patients referred for investigation of FI or CC in isolation were included. FACL was calculated at 5, 10, 20, 30, and 50 mm Hg above rectal pressure. 5th‐95th percentile in HV defined limits of normality.

Key Results

FACL was analyzed in 192 patients with FI (154 females), 204 patients with CC (175 females), and 134 HV (101 females). The optimal threshold for measurement of FACL was 20 mm Hg. Using this threshold, observer reproducibility was very high (ICC 0.99, P < 0.0001). FACL was shorter in females with FI and longer in females with CC compared to HV (2.3 vs 2.9 cm; and 3.4 cm vs 2.9 cm; both P < 0.0001). Twenty percent of females and 13% males with FI had a short FACL, associated with older age, anal hypotonia or hypocontractility, and a atrophic internal anal sphincter. However, abnormal FACL in isolation was only found in 1/190 FI (0.5%) and 2/201 CC (1%) patients; all other patients had other abnormal manometric findings.

Conclusions and Inferences

Considering overlap with other routinely evaluated manometric parameters, FACL measurement does not provide additional information in the diagnostic assessment of FI or CC.