bluuebunny/crossref_metadata_2025 huggingface dataset:
m6A-binding YTHDF proteins promote stress granule formation by modulating phase separation of stress granule proteins
Authors: Fu Ye , Zhuang Xiaowei
Published: July 2019

Diverse RNAs and RNA-binding proteins form phase-separated, membraneless granules in cells under stress conditions. However, the role of the prevalent mRNA methylation, m6A, and its binding proteins in stress granule (SG) assembly remain unclear. Here, we show that m6A-modified mRNAs are enriched in SGs, and that m6A-binding YTHDF proteins are critical for SG formation. Depletion of YTHDF1/3 inhibits SG formation and recruitment of m6A-modified mRNAs to SGs. Both the N-terminal intrinsically disordered region and the C-terminal m6A-binding YTH domain of YTHDF proteins are crucial for SG formation. Super-resolution imaging further reveals that YTHDF proteins are in a super-saturated state, forming clusters that reside in the periphery of and at the junctions between SG core clusters, and promote SG phase separation by reducing the activation energy barrier and critical size for condensate formation. Our results reveal a new function and mechanistic insights of the m6A-binding YTHDF proteins in regulating phase separation.
Benchmarking predictions of MHC class I restricted T cell epitopes
Authors: Paul Sinu , Croft Nathan P. , Purcell Anthony W. , Tscharke David C. , Sette Alessandro , Nielsen Morten , Peters Bjoern
Published: July 2019

T cell epitope candidates are commonly identified using computational prediction tools in order to enable applications such as vaccine design, cancer neoantigen identification, development of diagnostics and removal of unwanted immune responses against protein therapeutics. Most T cell epitope prediction tools are based on machine learning algorithms trained on MHC binding or naturally processed MHC ligand elution data. The ability of currently available tools to predict T cell epitopes has not been comprehensively evaluated. In this study, we used a recently published dataset that systematically defined T cell epitopes recognized in vaccinia virus (VACV) infected mice, considering both peptides predicted to bind MHC or experimentally eluted from infected cells, making this the most comprehensive dataset of T cell epitopes mapped in a complex pathogen. We evaluated the performance of all currently publicly available computational T cell epitope prediction tools to identify these major epitopes from all peptides encoded in the VACV proteome. We found that all methods were able to improve epitope identification above random, with the best performance achieved by neural network-based predictions trained on both MHC binding and MHC ligand elution data (NetMHCPan-4.0 and MHCFlurry). Impressively, these methods were able to capture more than half of the major epitopes in the top 0.04% (N = 277) of peptides in the VACV proteome (N = 767,788). These performance metrics provide guidance for immunologists as to which prediction methods to use. In addition, this benchmark was implemented in an open and easy to reproduce format, providing developers with a framework for future comparisons against new tools.

Author summary

Computational prediction tools are used to screen peptides to identify potential T cell epitope candidates. These tools, developed using machine learning methods, save time and resources in many immunological studies including vaccine discovery and cancer neoantigen identification. In addition to the already existing methods several epitope prediction tools are being developed these days but they lack a comprehensive and uniform evaluation to see which method performs best. In this study we did a comprehensive evaluation of publicly accessible MHC I restricted T cell epitope prediction tools using a recently published dataset of Vaccinia virus epitopes. We found that methods based on artificial neural network architecture and trained on both MHC binding and ligand elution data showed very high performance (NetMHCPan-4.0 and MHCFlurry). This benchmark analysis will help immunologists to choose the right prediction method for their desired work and will also serve as a framework for tool developers to evaluate new prediction methods.
Bifrost – Highly parallel construction and indexing of colored and compacted de Bruijn graphs
Authors: Holley Guillaume , Melsted Páll
Published: July 2019

Motivation

De Bruijn graphs are the core data structure for a wide range of assemblers and genome analysis software processing High Throughput Sequencing datasets. For population genomic analysis, the colored de Bruijn graph is often used in order to take advantage of the massive sets of sequenced genomes available for each species. However, memory consumption of tools based on the de Bruijn graph is often prohibitive, due to the high number of vertices, edges or colors in the graph. In order to process large and complex genomes, most short-read assemblers based on the de Bruijn graph paradigm reduce the assembly complexity and memory usage by compacting first all maximal non-branching paths of the graph into single vertices. Yet, de Bruijn graph compaction is challenging as it requires the uncompacted de Bruijn graph to be available in memory.

Results

We present a new parallel and memory efficient algorithm enabling the direct construction of the compacted de Bruijn graph without producing the intermediate uncompacted de Bruijn graph. Bifrost features a broad range of functions such as sequence querying, storage of user data alongside vertices and graph editing that automatically preserve the compaction property. Bifrost makes full use of the dynamic index efficiency and proposes a graph coloring method efficiently mapping eachk-mer of the graph to the set of genomes in which it occurs. Experimental results show that our algorithm is competitive with state-of-the-art de Bruijn graph compaction and coloring tools. Bifrost was able to build the colored and compacted de Bruijn graph of about 118,000 Salmonella genomes on a mid-class server in about 4 days using 103 GB of main memory.

Availability

https://github.com/pmelsted/bifrostavailable with a BSD-2 license

Contact

guillaumeholley@gmail.com
Macozinone: revised synthesis and crystal structure of a promising new drug for treating drug-sensitive and drug-resistant tuberculosis
Authors: Zhang Gang , Aldrich Courtney C.
Published: July 2019

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzothiazin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp
2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzothiazin-4-one group.
Two new CdII and ZnII coordination polymers incorporating 1-aminobenzene-3,4,5-tricarboxylic acid: synthesis, crystal structure and characterization
Authors: Shao Zhi-Chao , Meng Xiang-Ru , Hou Hong-Wei
Published: July 2019

Aminobenzoic acid derivatives are widely used in the preparation of new coordination polymers since they contain O-atom donors, as well as N-atom donors, and have a rich variety of coordination modes which can lead to polymers with intriguing structures and interesting properties. Two new coordination polymers incorporating 1-aminobenzene-3,4,5-tricarboxylic acid (H3abtc), namely, poly[(μ3-1-amino-5-carboxybenzene-3,4-dicarboxylato)diaquacadmium(II)], [Cd(C9H5NO6)(H2O)2]
n
, (I), and poly[[bis(μ5-1-aminobenzene-3,4,5-tricarboxylato)triaquatrizinc(II)] dihydrate], {[Zn3(C9H4NO6)2(H2O)3]·2H2O}
n
, (II), have been prepared and structurally characterized by single-crystal X-ray diffraction. In polymer (I), each tridentate 1-amino-5-carboxybenzene-3,4-dicarboxylate (Habtc2−) ligand coordinates to three CdII ions to form a two-dimensional network structure, in which all of the CdII ions and Habtc2− ligands are equivalent, respectively. Polymer (II) also exhibits a two-dimensional network structure, in which three crystallographically independent ZnII ions are bridged by two crystallographically independent pentadentate 1-aminobenzene-3,4,5-tricarboxylate (abtc3−) ligands. This indicates that changing the metal ion can influence the coordination mode of the H3abtc-derived ligand and further influence the detailed architecture of the polymer. Moreover, the IR spectra, thermogravimetric analyses and fluorescence properties were investigated.
Revival of traditional best practices for rangeland restoration under climate change in the dry areas
Authors: Ouled Belgacem Azaiez , Ben Salem Farah , Gamoun Mouldi , Chibani Roukaya , Louhaichi Mounir
Published: July 2019

Purpose

The purpose of this paper is to illustrate the benefits of reintroducing traditional grazing systems practices for improving arid rangelands. Grazing is the most extensive land use in southern Tunisia, but the rangelands have suffered many decades of severe degradation due to profound socioeconomic changes and the emergence of an agro-pastoral society in place of the former pastoral one. Traditional grazing systems (gdel and herd mobility), which had historically allowed for grazing deferment and control of grazing livestock were abandoned. Yet grazing management strategies are important tools to sustain integrated livestock rangeland production systems in dry areas in the face of ongoing climate change and human pressure.

Design/methodology/approach

This study assesses the revival of traditional best practices of rangeland resting in a representative community. Total plant cover, species composition, flora richness and range production were determined in six rangeland sites subjected respectively to one, two and three years of rest; one and two years of light grazing after rest; and free grazing (control).

Findings

Results showed that dry rangelands keep their resilience to the negative effects of climate change once human pressure is controlled. A maximum of two years of rest is enough to sustainably manage the rangelands in southern Tunisia, as this protection showed considerable and positive effects on the parameters scored.

Originality/value

The revival of the traditional best practices under new arrangements adapted to current biophysical and socioeconomic conditions would be an excellent tool to mitigate the negative effects of frequent droughts and reduce the animal feed costs that poor farmers face.
Optimization of texture geometry for a rotating ring to maximum load-carrying capacity
Authors: Tian Zaihao , Ma Jin-Kui , Changhou Lu , Chen Shu-Jiang
Published: July 2019

Purpose

The purpose of this paper is to maximize the load-carrying capacity (LCC) of a rotating ring, a numerical model optimizing both the surface and bottom shape of its surface textures is proposed.

Design/methodology/approach

The Reynolds equation is used to evaluate the film pressure and LCC obtained by integrating the film pressure is set as the objective function. Around the center of the computational domain, radial lines with an equal angle between adjacent ones are produced and the surface contour of textures is obtained by connecting the endpoints using a spline curve. The bottom profile is then obtained by connecting the endpoints of two vertical lines at the circumferential ends of textures. Lengths of these lines are set as design variables and genetic algorithm is used to solve optimization models.

Findings

Results show that optimum textures have an “apple-like” surface contour and a “wedge-like” bottom profile, which are both expressed by smooth spline curves. Optimum wedge-bottom textures generate higher LCC than optimum flat-bottom textures. Moreover, the optimum textures have the highest LCC compared with optimum grooves proposed previously, which validates the practical value of the current optimization model.

Originality/value

This work presents a comprehensive optimization method of texture geometry, which provides a new idea of the design of surface textures.
Signs of Safety: lessons learnt from evaluations
Authors: Baginsky Mary , Moriarty Jo , Manthorpe Jill
Published: July 2019

Purpose

Signs of Safety (SoS) is a strengths-based approach to child protection casework that has been widely adopted in countries across the world. The purpose of this paper is to report on a study that aimed to synthesise the many evaluations of SoS that have been conducted to assess their strengths and limitations. The intention is to identify the aspects which should be explored further and those that remain unexamined to inform future evaluations.

Design/methodology/approach

The study collated and then examined many of the evaluations that are in the public domain as well as some of those that were conducted within agencies and have not been made publicly available.

Findings

At the present time (early 2019), the evidence base for SoS is limited. Independent, robust research needs to be undertaken over time to build on the studies that have been conducted. New research must be designed to fill gaps and be capable of producing the evidence required and it must address its own limitations.

Originality/value

This study is the most comprehensive contemporary review of the evaluations of SoS that have been conducted to the best of the authors’ knowledge.
Time-varying response of treasury yields to monetary policy shocks
Authors: Mbarek Lassaâd , Marfatia Hardik A. , Juko Sonja
Published: July 2019

Purpose

This paper aims to examine the Treasury bond yields response to monetary policy shocks in Tunisia under a heterogeneous economic environment.

Design/methodology/approach

Using a traditional fixed coefficient model, the impact of monetary policy changes on the term structure of interest rates for the whole period from January 2006 to December 2016 is estimated first. Then the stability of this relationship by distinguishing two sub-periods around the revolution of January 2011 is studies. To investigate how the relationship between the monetary policy and the Treasury yield curve evolves over time, a time-varying parameter model is estimated.

Findings

The results show that the impact of monetary policy is more pronounced at the short end of the yield curve relative to the longer end. Furthermore, this impact declines significantly across all maturities following the revolution and exhibits wide time variation. This evidence supports the negative influence of high levels of uncertainty on monetary policy effectiveness and highlights the desirability of more active monetary policy, especially in turbulent environment.

Research limitations/implications

The impact of uncertainty on the effectiveness of monetary policy shocks needs to be explored further in future research to understand the structural sources of uncertainty and their dynamic interactions with monetary policy and risk aversion in asset markets.

Practical implications

A more active role of the central bank to influence the yield curve mainly through Treasury bond purchases covering medium and long maturities may be warranted. Communication also needs to be reinforced to ensure predictability of the monetary policy stance.

Originality/value

This paper extends the empirical literature on the pass-through of monetary policy to interest rates for an emerging country in context of transition by estimating a state-space model to test the time-varying behavior and examine the influence of increased economic uncertainty on monetary policy effectiveness.
Risk models vs characteristic models from an investor’s perspective
Authors: Fieberg Christian , Varmaz Armin , Poddig Thorsten
Published: July 2019

Purpose

The purpose of this paper is to analyze the implications of the risk versus characteristic debate from the perspective of a mean-variance investor.

Design/methodology/approach

Expected returns and the variance-covariance matrix are estimated based on various characteristic and risk models and evaluated for the purpose of mean-variance portfolios.

Findings

Return estimates from characteristic models are most informative to investors. Risk-factor models provide the most informative estimates of the risk. A mean-variance investor should rely on combinations of the two model types.

Originality/value

Although the risk vs characteristic debate is a binary academic debate, our findings from an investor's perspective suggest to make use of the best of both worlds.
The effect of consumer emotions on outcome behaviors following service failure
Authors: Harrison-Walker L. Jean
Published: July 2019

Purpose

The purpose of this paper is to explore the role of emotions that consumers experience following service failures and to assess the effects of each of these emotions on important behavioral outcomes.

Design/methodology/approach

This paper extends the work of Wetzer et al. (2007) and draws upon the existing literature to test a series of research hypotheses tying emotions to four important behavioral outcomes primarily using stepwise regression.

Findings

When a service failure occurs, customers experience any of a variety of negative emotions. The effect on behavioral outcomes depends on the specific emotion experienced by the consumer. The current research, which benefits by using retrospective experience sampling, finds that frustration is the predominant emotion experienced by customers following service failure, but that anger, regret and frustration affect behavioral outcomes. Uncertainty also plays a role.

Research limitations/implications

Future research should investigate the antecedents of propensity for emotions and predisposition toward industries, as well as the consequences of word-of-mouth (WOM) praise and WOM activity. Additionally, emotions could be examined by service stage. Several other moderators could be investigated, including severity, complaining behavior, repeat occurrence, service importance, remedies and forgiveness, product vs process failures, tenure, gender and age.

Practical implications

The current research emphasizes the importance of understanding which emotion is being experienced by a customer following service failure to identify the behavioral outcomes that will be most impacted. The specific managerial implications depend upon the specific emotional response experienced by the customer and are discussed separately for anger, regret and frustration. Service personnel must be trained to recognize and address specific customer emotions rather than to provide a canned or generalized response.

Originality/value

To date, there has been little, if any, systematic research into the effects of multiple discrete negative emotions on multiple desirable behavioral outcomes. The current study examines six discrete emotions. Predominant emotions are differentiated from emotional intensity. The behavioral outcomes of reconciliation and reduced share-of-wallet are added to the traditional outcomes of repatronage intentions and negative WOM. While existing research tends to rely on a scenario approach, this study uses the retrospective experience sampling method. The authors distinguish between mixed emotions and multiple emotions. The relative effects of disappointment and regret are examined for each of the four outcomes. Finally, importance-performance map analysis was applied to the findings to prioritize managerial attention. Numerous managerial and research implications are identified.
System dynamics models for the simulation of sustainable urban development
Authors: Pejic Bach Mirjana , Tustanovski Emil , Ip Andrew W.H. , Yung Kai-Leung , Roblek Vasja
Published: July 2019

Purpose

System dynamics is a whole-system modelling and learning approach, useful for tackling non-linear problems, such as sustainable urban development. The purpose of this paper is to review system dynamics applications in the simulation of sustainable urban development over a period from 2005 to 2017.

Design/methodology/approach

The analysis reveals that the number of applications of system dynamics modelling in the area of urban sustainable development increased in the analysed period. Research has changed its focus from the modelling of environmental problems to more complex models, portraying the multidimensional socio-economic processes that have an impact on the sustainability of urban development. Analysed case studies most often use the behaviour reproduction test for model validation, but without a unified approach. In most cases, modelling has been done in China, Germany and the USA, while urban development in the Eastern European countries, Africa and Latin America has not often been investigated. This paper indicates the knowledge gaps and suggests future research directions.

Findings

Papers that report the use of system dynamics modelling reveal a wide range of applications in urban sustainability. The analysis shows significant emphasis on environmental problems, while the interest for modelling social problems has been increasing during the last several years. Most of the modelled problems examine the sustainability of resources (land, water) and waste management, which are used for insights into the reasons for the system behaviour, forecasting future behaviour and policy testing.

Originality/value

The presented models were developed in most cases for the purpose of understanding the phenomena examined, as well as the future use of the models in policy planning. This brings us back to the need for greater stakeholder involvement, not only in the initial phase, but also during the whole modelling process, which could increase understanding, use and ownership of the models in the future, and thus increase their practical application.
User experience of e-government: the Nigeria Immigration Service
Authors: Okunola Olaseni Muritala , Rowley Jennifer
Published: July 2019

Purpose

The purpose of this paper is to identify key considerations influencing the adoption and use of e-government services by providing insights into users’ views of their experience of an e-government service in a developing country, the website of the Nigeria Immigration Service (NIS).

Design/methodology/approach

An online questionnaire-based survey was conducted to capture perceptions of the user experience with the NIS website. Descriptive statistics for each of the factors that contribute to the user experience are reported and discussed, with reference to open comments and previous literature. These factors are security and support, trust, ease of use, website quality, content and information, perceived benefits, convenience and perceived barriers.

Findings

There is strong evidence of concern in relation to the security of financial transactions, the use of personal data and trustworthiness, which is aggravated by inadequate user support. There is a lack of consensus regarding ease of use, website quality and content and information. In terms of barriers and benefits, there was a general agreement that the website offered greater convenience than alternative channels, but some concerns were identified regarding the reliability of technology, and, for users in Nigeria, the reliability of the electricity supply.

Originality/value

This paper adds to the very sparse literature on e-government in Nigeria, as well as extending consideration of the public value approach to e-government in developing countries.
Anti-psychotic medication decision making during pregnancy: a co-produced research study
Authors: Pinfold Vanessa , Dare Ceri , Hamilton Sarah , Kaur Harminder , Lambley Ruth , Nicholls Vicky , Petersen Irene , Szymczynska Paulina , Walker Charlotte , Stevenson Fiona
Published: July 2019

Purpose

The purpose of this paper is to understand how women with a diagnosis of schizophrenia or bipolar disorder approach medication decision making in pregnancy.

Design/methodology/approach

The study was co-produced by university academics and charity-based researchers. Semi-structured interviews were conducted by three peer researchers who have used anti-psychotic medication and were of child bearing age. Participants were women with children under five, who had taken anti-psychotic medication in the 12 months before pregnancy. In total, 12 women were recruited through social media and snowball techniques. Data were analyzed following a three-stage process.

Findings

The accounts highlighted decisional uncertainty, with medication decisions situated among multiple sources of influence from self and others. Women retained strong feelings of personal ownership for their decisions, whilst also seeking out clinical opinion and accepting they had constrained choices. Two styles of decision making emerged: shared and independent. Shared decision making involved open discussion, active permission seeking, negotiation and coercion. Independent women-led decision making was not always congruent with medical opinion, increasing pressure on women and impacting pregnancy experiences. A common sense self-regulation model explaining management of health threats resonated with women’s accounts.

Practical implications

Women should be helped to manage decisional conflict and the emotional impact of decision making including long term feelings of guilt. Women experienced interactions with clinicians as lacking opportunities for enhanced support except in specialist perinatal services. This is an area that should be considered in staff training, supervision, appraisal and organization review.

Originality/value

This paper uses data collected in a co-produced research study including peer researchers.
Twenty‐four‐week interim analysis from a phase 3 open‐label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa
Authors: Morita Akimichi , Takahashi Hidetoshi , Ozawa Kentaro , Imafuku Shinichi , Nakama Takekuni , Takahashi Kenzo , Matsuyama Takashi , Okubo Yukari , Kitamura Susumu , Matsuda Naoto , Zhao Yiwei , Yokoyama Masayuki , Hayashi Nobukazu , Terui Tadashi
Published: July 2019

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor‐α, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open‐label, single‐arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patients with moderate to severe HS. Fifteen patients received adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week thereafter starting at week 4. The fulfillment of Hidradenitis Suppurativa Clinical Response was assessed under adalimumab treatment; clinical response was assessed by skin pain, total abscess and inflammatory nodule count and modified Sartorius score; and quality of life and safety were assessed. At week 12, 86.7% of patients achieved clinical response, with improvements at week 12 across the primary and secondary end points generally sustained through week 24. Adalimumab weekly dosing was generally safe and well tolerated with no new safety findings through week 24. These results suggest that adalimumab is effective and well tolerated in Japanese patients with moderate to severe HS.
Germination timing and chilling exposure create contingency in life history and influence fitness in the native wildflower Streptanthus tortuosus
Authors: Gremer Jennifer R. , Wilcox Chenoa J. , Chiono Alec , Suglia Elena , Schmitt Johanna
Published: July 2019

The timing of life history events, such as germination and reproduction, influences ecological and selective environments throughout the life cycle. Many organisms evolve responses to seasonal environmental cues to synchronize these key events with favourable conditions. Often the fitness consequences of each life history transition depend on previous and subsequent events in the life cycle. If so, shifts in environmental cues can create cascading effects throughout the life cycle, which can influence fitness, selection on life history traits, and population viability.

We examined variation in cue responses for contingent life history expression and fitness in a California native wildflower, Streptanthus tortuosus, by manipulating seasonal germination timing in a common garden experiment. We also manipulated chilling exposure to test the role of vernalization cues for seasonal life history contingency.

Plants germinating early in the growing season in autumn were more likely to flower in the first year and less likely to perennate than later germinants in spring. First‐year reproduction and overall fitness was the highest for autumn cohorts. Sensitivity analyses showed that optimal germination date depended on survival beyond the first year and fruit production in later years.

Experimental chilling exposure induced first‐year flowering in spring germinants, demonstrating that seasonal life history contingency is mediated by a vernalization requirement. This requirement reduced fitness of spring germinants without increasing survival or later fecundity and may be maladaptive. Such mismatches between cues and fitness may become more pervasive as predicted climate change reduces exposure to chilling, shortens growing seasons, and increases severity of summer drought.

Synthesis. Shifts in germination timing in seasonal environments can cause cascading effects on trait expression and fitness that extend beyond the first year of the life cycle. Climate change is likely to shift seasonal conditions, influencing such life history contingency, with significant impacts on trait expression, fitness, and population persistence. These shifts may cause strong natural selection on cue sensitivity and life history expression, but it is an open question whether populations have the potential for rapid adaptation in response to this selection.
Spatial variations of soil silicon availability and biogenic silicon flux in a lowland tropical forest in Malaysia
Authors: Ishizawa Hidehiro , Niiyama Kaoru , Iida Yoshiko , Shari Nur H. Z. , Ripin Azizi , Kitajima Kaoru
Published: July 2019

Tropical tree species differ widely in their silicon (Si) accumulation patterns, but the implications of such species differences for ecosystem Si flux remain unexplored. We analyzed how biogenic Si flux via leaf litter and soil Si availability in the upper soil vary spatially within a 2 ha area in a lowland Dipterocarp forest in Peninsular Malaysia. Silicon concentration per unit leaf dry mass of 86 dominant tree species in this plot ranged from 0.4 to 126 mg/g. Soil Si availability at 100 sampling points and Si flux via leaf litter at 66 litter traps showed large variations up to 3.3‐ and 17.9‐folds, respectively. However, they correlated neither with each other nor with the expected Si flux from tree species composition in the neighborhood. When we classified tree species to four groups by their leaf Si concentrations (negligible, low, moderate and high), tree species with moderate leaf Si concentrations were significantly more abundant on Si‐rich soils. In contrast, the other three groups did not show any significant spatial relationships with soil Si availability. These results indicate that soil Si availability, Si accumulation by vegetation and Si flux via leaf litter show wide spatial variations in a lowland tropical forest, without a simple relationship with each other.
Optimization of Headspace Solid‐Phase Microextraction (HS‐SPME) Parameters for the Analysis of Pyrazines in Yeast Extract via Gas Chromatography Mass Spectrometry (GC‐MS)
Authors: Raza Ali , Begum Nabila , Song Huanlu , Li Ku , Li Pei
Published: July 2019

Yeast extract was analyzed through headspace solid‐phase microextraction (HS‐SPME) in combination with (GC‐MS) for its pyrazine compounds. Four different types of SPME fibers with various polarities were selected for preoptimization. The three coated fiber 50/30 µm DVB/CAR/PDMS showed the maximum volatile extraction efficiency and was selected for further analysis. Twenty‐eight volatile compounds were tentatively identified through GC‐MS including eight pyrazines and were categorically characterized as major volatile compounds responsible for the flavor enhancing notes in YE. Response surface methodology encoded with face centered central composite design was employed to optimize the experimental design. Average peak area of selected pyrazines; methylpyrazine, 2,3‐dimethylpyrazine, 2,6‐dimethylpyrazine, 2‐ethyl‐5‐methylpyrazine, trimethylpyrazine, 3‐ethyl‐2,5‐dimethylpyrazine, tetramethylpyrazine, 3,5‐diethyl‐2‐methylpyrazine, and 2,3,5‐trimethyl‐6‐ethylpyrazine were optimized through RSM‐CCD to get the best conditions for HS‐SPME. The HS‐SPME variables X1 (equilibrium time), X2 (extraction time), and X3 (extraction temperature) were programed into the run sheets to opt an optimistic statistical approach. Among these, the variable X2 and X3 showed the most significant results with the response variable R and could be concluded as the most tantalize variables while practicing pyrazines extraction through HS‐SPME method. Resultantly, the optimization methodology was successfully applied for the extraction of pyrazines from yeast extract.

Practical Application

The selection of optimal conditions to conduct a HS‐SPME experiment can dramatically affect the sensitivity and accuracy of aroma extraction process. Optimizing the SPME conditions is the best way to identify the role of all the possible factors that can fluctuate the volatile profile of any sample. This type of statistical approach to optimize the HS‐SPME conditions for pyrazines in yeast extract was practiced for the very first time and could be considered as a prerequisite strategy to proliferate future projects related to some novel studies in terms of pyrazines flavor perception.
Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single‐center experience
Authors: Barut Kenan , Adrovic Amra , Sahin Sezgin , Tarcin Gurkan , Tahaoglu Gulberk , Koker Oya , Yildiz Mehmet , Kasapcopur Ozgur
Published: July 2019

Aim

Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long‐term treatment response and disease complications in a large sJIA cohort.

Methods

Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long‐term treatment response and disease complications were retrospectively collected.

Results

A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection.

Conclusion

The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.
Prohibiting Autonomous Weapons: Put Human Dignity First
Authors: Rosert Elvira , Sauer Frank
Published: July 2019

In addition to its successful mobilization in stigmatization and norm‐setting processes on anti‐personnel landmines and cluster munitions, the principle of distinction as enshrined in International Humanitarian Law also figures prominently in the debate on lethal autonomous weapons systems (LAWS). Proponents of a ban on LAWS frame these as indiscriminate, that is, unable to distinguish between civilians and combatants, and thus as inherently unlawful. The flip side of this particular legal argument is, however, that LAWS become acceptable when considered capable of distinguishing between combatants and civilians. We thus argue, first, that this particular legal basis for the call for a ban on LAWS might be rendered obsolete by technological progress increasing discriminatory weapon capabilities. Second, we argue that the argument is normatively troubling as it suggests that, as long as civilians remain unharmed, attacking combatants with LAWS is acceptable. Consequently, we find that the legal principle of distinction is not the overall strongest argument to mobilize when trying to stigmatize and ban LAWS. A more fundamental, ethical argument within the debate about LAWS – and one less susceptible to ‘technological fixes’ – should be emphasized instead, namely that life and death decisions on the battlefield should always and in principle be made by humans only.
Open Plurilateral Agreements, International Regulatory Cooperation and theWTO
Authors: Hoekman Bernard , Sabel Charles
Published: July 2019

Sustained high growth in many developing countries (‘the rise of the rest’) combined with long‐standing World Trade Organization (WTO) working practices hamper the ability of theWTOto perform its routine functions and paralyze efforts to adapt to new circumstances. For want of an alternative, preferential trade agreements have taken up some of the slack in addressing differences in domestic regulation of product safety, environmental and social conditions, but these are exclusionary and inefficient from a global perspective. In this article, we argue that a new type of agreement based on open plurilateral cooperation offers better prospects for groups of countries to explore and develop their potential common interests on regulatory matters, while safeguarding core aspects of their national regulatory sovereignty and increasing the possibility of regenerating theWTOfrom within.
ThermStats: An R package for quantifying surface thermal heterogeneity in assessments of microclimates
Authors: Senior Rebecca A. , Hill Jane K. , Edwards David P.
Published: July 2019

Variation in temperature at a fine spatial scale creates critically important microclimates for many organisms. Quantifying thermal heterogeneity at this scale is challenging and, until recently, has been largely restricted to the use of dataloggers to record air temperature. Thermography is becoming an increasingly viable alternative. A single photo from a thermal imaging camera contains thousands of spatially explicit surface temperature measurements, making thermal cameras ideal for rapidly assessing temperature variation at fine scale.

Here, we present an R package—ThermStats—for processing thermal images and other gridded temperature data. The package addresses current constraints on applying thermography in ecology, by speeding up and simplifying the extraction of data from thermal images, and by facilitating the calculation of different metrics of thermal heterogeneity. The metrics capture both the frequency distribution and spatial patterns of temperature, and the package functions are designed to accommodate different sampling strategies and data in either matrix or raster format.

We demonstrate how ThermStats can be used to capture temperature variation at fine spatial scales in structurally complex habitat, such as tropical rainforest. Using thermal images collected in the field (~0.5 cm2 resolution), we found that thermal hetereogeneity varied little between primary and logged forest, but did vary with time of day. Comparing temperature extremes in a microclimate layer estimated from LIght Detection And Ranging data (LIDAR; 2,500 m2 resolution) , we found that both hot and cold extremes were hotter inside oil palm plantations than in the neighbouring forest.

Our package simplifies the processing of thermal data, and our metrics capture key spatiotemporal temperature trends that underpin physiological, behavioural and demographic responses to environmental change. As such, ThermStats can advance a wide range of studies requiring fine‐scale surface temperature data for microclimate investigations.
Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial—Protocol and statistical analysis plan
Authors: Meyhoff Tine Sylvest , Hjortrup Peter Buhl , Møller Morten Hylander , Wetterslev Jørn , Lange Theis , Kjær Maj‐Brit Nørregaard , Jonsson Andreas Bender , Hjortsø Carl Johan Steensen , Cronhjort Maria , Laake Jon Henrik , Jakob Stephan M. , Nalos Marek , Pettilä Ville , van der Horst Iwan , Ostermann Marlies , Mouncey Paul , Rowan Kathy , Cecconi Maurizio , Ferrer Ricard , Malbrain Manu L. N. G. , Ahlstedt Christian , Hoffmann Søren , Bestle Morten Heiberg , Nebrich Lars , Russell Lene , Vang Marianne , Rasmussen Michael Lindhardt , Sølling Christoffer , Rasmussen Bodil Steen , Brøchner Anne Craveiro , Perner Anders
Published: July 2019

Introduction

Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock.

Methods

CLASSIC trial is an investigator‐initiated, international, randomised, stratified, and analyst‐blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health‐related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre‐defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention‐to‐treat (ITT) population.

Discussion

The CLASSIC trial results will provide important evidence to guide clinicians’ choice regarding the IV fluid therapy in adults with septic shock.
Storage time of red blood cells among ICU patients with septic shock
Authors: Rygård Sofie L. , Grønlykke Lars , Perner Anders , Winkel Per , Lange Theis , Broksø Holst Lars , Johansson Pär I. , Aneman Anders , Brodersen Thorsten , Laurén Eva , Ullum Henrik , Wetterslev Jørn
Published: July 2019

Background

We aimed to describe the exposure to blood transfusions and mortality among patients with septic shock.

Methods

We did a retrospective cohort study of two cohorts—patients with septic shock registered in a Danish ICU database (2008‐2010) and patients from the Transfusion Requirements in Septic Shock (TRISS) trial (2011‐2013). We extracted information on blood transfusions issued to all patients. We investigated the number of patients receiving very fresh blood (less than 7 days), very old blood (more than 24 days) and blood with a mixture of storage time.

Results

In the Danish cohort, 1637 patients were included of whom 1394 (85%) received 20,239 blood units from 14 days prior the ICU admission to 90 days after; 33% were transfused before, 77% in the ICU and 36% after ICU. The exposure to exclusively very fresh or very old blood was 3% and 4%, respectively.

In the TRISS cohort, 77% of the 937 patients received 5047 RBC units; 3% received exclusively very fresh and 13% very old blood. The point estimate of mortality was higher among patients receiving large amounts of exclusively very fresh and very old blood, but the number of patients were very small.

Conclusions

Patients with septic shock were transfused both before and after ICU. Exposure to blood of less than 7 days or more than 24 days old were limited. We were not able to detect higher mortality among the limited number of patients with septic shock transfused with very fresh or very old blood.
Alcohol Consumption in Later Life and Mortality in the United States: Results from 9 Waves of the Health and Retirement Study
Authors: Keyes Katherine M. , Calvo Esteban , Ornstein Katherine A. , Rutherford Caroline , Fox Matthew P. , Staudinger Ursula M. , Fried Linda P.
Published: July 2019

Background

Alcohol consumption in later life has increased in the past decade, and the relationship between alcohol consumption and mortality is controversial. Recent studies suggest little, if any, health benefit to alcohol. Yet most rely on single–time point consumption assessments and minimal confounder adjustments.

Methods

We report on 16 years of follow‐up from the Health and Retirement Study (HRS) cohorts born 1931 to 1941 (N = 7,904, baseline mean age = 61, SD = 3.18). Respondents were queried about drinking frequency/quantity. Mortality was established via exit interviews and confirmed with the national death index. Time‐varying confounders included but were not limited to household assets, smoking, body mass index, health/functioning, depression, chronic disease; time‐invariant confounders included baseline age, education, sex, and race.

Results

After adjustment, current abstainers had the highest risk of subsequent mortality, consistent with sick quitters, and moderate (men: HR = 0.74, 95% CI: 0.60 to 0.91; women: HR = 0.82, 95% CI: 0.63 to 1.07) drinking was associated with a lower mortality rate compared with occasional drinking, though smokers and men evidenced less of an inverse association. Quantitative bias analyses indicated that omitted confounders would need to be associated with ~4‐fold increases in mortality rates for men and ~9‐fold increases for women to change the results.

Conclusions

There are consistent associations between moderate/occasional drinking and lower mortality, though residual confounding remains a threat to validity. Continued efforts to conduct large‐scale observational studies of alcohol consumption and mortality are needed to characterize the changing patterns of consumption in older age.