bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Colloidal Microstructures of β-Escin and the Liposomal
Components Cholesterol and DPPC
Authors: de Groot Carolin , Müsken Mathias , Müller-Goymann Christel 
Published: May 2018

AbstractThe discovery of immunostimulating complex formation by the saponin Quil A from
the plant Quillaja saponaria with cholesterol and a phospholipid opened
up new avenues for the development of drug delivery systems for vaccine
application with additional adjuvant properties. In this study, β-escin,
a monodesmosidic triterpene saponin from horse chestnut, was investigated in
terms of its interaction with liposomal components (cholesterol,
dipalmitoylphosphatidylcholine) by Langmuir film balance studies and with regard
to particle formation visualized by transmission electron microscopy. A strong
interaction of β-escin with cholesterol was observed by Langmuir
isotherms due to the intercalation of the saponin into the monolayer, whereas no
interaction occurred with dipalmitoylphosphatidylcholine. Transmission electron
microscopy studies also confirmed the strong interaction of β-escin with
cholesterol. In aqueous pseudo-ternary systems (β-escin,
dipalmitoylphosphatidylcholine, cholesterol) and in pseudo-binary systems
(β-escin, cholesterol), new colloidal structures built up from
ring-like and worm-like subunits were observed with a size of about
100 – 200 nm. These colloidal structures are formed in pseudo-binary systems by
aggregation of the subunits, whereas in pseudo-ternary systems, they are formed
among others by attacking the liposomal membrane. The rehydration of the
liposomal dispersions in NANOpure water or Tris buffer pH 7.4 (140 mM) resulted
in the same particle formation. In contrast, the sequence of the dispersionsʼ
production process affected the particle formation. Unless adding the saponin to
the other components from the beginning, just a liposomal dispersion was formed
without any colloidal aggregates of the subunits mentioned above.
Ethnobotany and Medicinal Plant Biotechnology: From Tradition to
Modern Aspects of Drug Development
Authors: Kayser Oliver 
Published: May 2018

AbstractSecondary natural products from plants are important drug leads for the
development of new drug candidates for rational clinical therapy and exhibit a
variety of biological activities in experimental pharmacology and serve as
structural template in medicinal chemistry. The exploration of plants and
discovery of natural compounds based on ethnopharmacology in combination with
high sophisticated analytics is still today an important drug discovery to
characterize and validate potential leads. Due to structural complexity, low
abundance in biological material, and high costs in chemical synthesis,
alternative ways in production like plant cell cultures, heterologous
biosynthesis, and synthetic biotechnology are applied. The basis for any
biotechnological process is deep knowledge in genetic regulation of pathways and
protein expression with regard to todays “omics” technologies. The high number
genetic techniques allowed the implementation of combinatorial biosynthesis and
wide genome sequencing. Consequently, genetics allowed functional expression of
biosynthetic cascades from plants and to reconstitute low-performing pathways in
more productive heterologous microorganisms. Thus, de novo biosynthesis
in heterologous hosts requires fundamental understanding of pathway
reconstruction and multitude of genes in a foreign organism. Here, actual
concepts and strategies are discussed for pathway reconstruction and genome
sequencing techniques cloning tools to bridge the gap between
ethnopharmaceutical drug discovery to industrial biotechnology.
Does maximalist footwear lower impact loading during level ground and downhill running?
Authors: Chan Zoe Y. S. , Au Ivan P. H. , Lau Fannie O. Y. , Ching Eric C. K. , Zhang Janet H. , Cheung Roy T. H. 
Published: May 2018

AbstractA new model of running shoes which features an extreme cushioning and an oversized midsole, known as the maximalist (MAX) was launched. This design claims to provide excellent shock absorption, particularly during downhill running. This study sought to assess the effects of MAX on the external impact loading, footstrike pattern, and stride length during level ground and downhill running on an instrumented treadmill. Twenty‐seven distance runners completed four 5‐minute running trials in the two footwear conditions (MAX and traditional running shoes (TRS)) on a level surface (0%) and downhill (10%‐declination). Average and instantaneous loading rates (ILRs), footstrike pattern and stride length were measured during the last minute of each running trial. A 12% greater ILR was observed in downhill running with MAX (p = .045; Cohen's d = 0.44) as compared to TRS. No significant difference was found in the loading rates (p > .589) and stride length (p = .924) when running on a level surface. Majority of runners maintained the same footstrike pattern in both footwear conditions. Findings of this study suggested that MAX might not reduce the external impact loading in runners during level and downhill treadmill running. Instead, this type of footwear may conceivably increase the external impact loading during downhill treadmill running.
The influence of hold regularity on perceptual‐motor behaviour in indoor climbing
Authors: Button Chris , Orth Dominic , Davids Keith , Seifert Ludovic 
Published: May 2018

AbstractClimbers often train on indoor climbing walls, which are modifiable to simulate features of outdoor climbing environments at different levels of difficulty. The aim of this study was to evaluate the influence of regularity of climbing holds on emergent perceptual‐motor behaviours. Skilled climbers performed six repetitions of two topographically similar routes on an indoor climbing wall. One route was composed of 18 different types of hand holds (irregular route), whereas the other route had only two types of hand holds (regular route). Preview and climbing durations, as well as visual search behaviours, were recorded. Participants rated the regular route as more difficult to climb, requiring greater perceived effort to complete. The time spent previewing, and then climbing the routes, was reduced on average by 12% and 16%, respectively in the irregular route compared to the regular route. There were more fixations made when climbing the regular route (281 vs. 222 fixations per trial). It seems the climbers were more careful and thorough in their gaze behaviours with the regular route because of the additional technical demands it presented, whereas the irregular route afforded a more superficial visual exploration with use of more frequent saccades between holds. The findings suggest how irregularity in the environment is exploited by skilled climbers, apparently making the practice context easier to perceive and act in.
Demography: A Very Short Introduction
Authors: Harper Sarah 
Published: May 2018

Abstract
Demography—the study of people—addresses the size, distribution, composition, and density of populations, and considers the impact these factors have on individual lives and the changing structure of human populations. Each generation’s demographic composition influences a person’s life chances; the economic and political structures within which that life is lived; the person’s access to social and natural resources; and life expectancy. Demography: A Very Short Introduction considers how the global population has evolved over time and space and discusses the theorists, theories, and methods involved in studying population trends and movements. It also looks at the emergence of new demographic sub-disciplines and addresses some of the future population challenges.
Sub-disciplines arise
Authors: Harper Sarah 
Published: May 2018

Abstract
While most of the social science disciplines deal with people, some have developed a specific interest in demographic analysis and demographic theories, and these have been formalized into sub-disciplines of demography. In many cases they represent a merging of an area within the main discipline of demography. ‘Sub-disciplines arise’ looks at several of these sub-disciplines in turn: anthropological demography, bio-demography, economic demography (or population economics), family demography, historical demography, mathematical demography, palaeodemography, population geography (or spatial demography), population studies, and social demography. These all now form part of a broad field of population studies that analyse the relationships between economic, social, cultural, and biological processes influencing a population.
The reign of terror
Authors: Townshend Charles 
Published: May 2018

Abstract
What are the origins of terrorism? ‘The reign of terror’ explains that the notion of terrorism, or terror, came from the French Revolution. The terror transformed the Revolution from a liberating to a destructive force. Those who instigated the terror had to find justification for their violent killing. Their motivation provides a key to the distinctive nature of modern terrorism. The revolutionaries may have seemed to act as crusaders, but the Reign of Terror was informed by the Enlightenment assumption that human agency can change the social order. The French Revolution’s use of violence created a model for the application of terrorizing force by state actors that lasted two centuries.
Revolutionary terrorism
Authors: Townshend Charles 
Published: May 2018

Abstract
The word ‘revolutionary’ has been applied over the last century in three social-political contexts: within existing nation-states; in external colonial situations; and in ‘internal colonial’ situations where ethnic groups are oppressed by a majority group within a single area. ‘Revolutionary terrorism’ explores contrasting motives for revolution: social transformation, assertion of ethnic identity, and progressive ideology. Terrorism can be divided into two ages: the late 19th century to early 20th century, where the aim was to seize political power from the established regime to bring about profound political and social change; and the early 20th century onwards, on the sidelines of political action, a terrorism of resistance.
Nationalism and terror
Authors: Townshend Charles 
Published: May 2018

Abstract
The framework for much of modern terrorist action is ethnic or nationalist, with each nationalism being culturally unique. The emblematic terrorist act—the assassination of Archduke Franz Ferdinand in June 1914—was a nationalist act. Nationalist movements have shown greater resilience than smaller left-wing revolutionary groups. Nationalism is a very strong force, so even a nation whose struggle seems likely to fail, such as the Chechens, may never give up. ‘Nationalism and terror’ looks at how nationalists have used terror to fight their cause, illustrating this with the case studies of the Irish republican IRA, the Basque separatists ETA, and Zionists in Palestine. Can terror liberate nations?
Countering terrorism
Authors: Townshend Charles 
Published: May 2018

Abstract
What can be done about terrorism? The multiplicity of possible responses range from mild regulation to full-blooded military repression, but what are the possible benefits and what are the likely costs? ‘Countering terrorism’ considers the differences between antiterrorist and counterterrorist measures, looking at the pros and cons in impulsive, appropriate, and long-term responses to terrorist acts, especially in light of recent terrorist attacks in European cities; and discusses democracy against terrorism and the balance between freedom and security. It is unlikely that terrorism will ever end, but the belief is that it is no more likely to bring about the destruction of Western civilization than it was a century ago.
Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: an individual participant data meta-analysis
Authors: Blom J W , Van den Hout W B , Den Elzen W P J , Drewes Y M , Bleijenberg N , Fabbricotti I N , Jansen A P D , Kempen G I J M , Koopmans R , Looman W M , Melis R J F , Metzelthin S F , Moll van Charante E P , Muntinga M E , Numans M E , Ruikes F G H , Spoorenberg S L W , Stijnen T , Suijker J J , De Wit N J , Wynia K , Wind A W , Gussekloo J ,   TOPICS-MDS research consortium
Published: May 2018

Abstract

Purpose
to support older people with several healthcare needs in sustaining adequate functioning and independence, more proactive approaches are needed. This purpose of this study is to summarise the (cost-) effectiveness of proactive, multidisciplinary, integrated care programmes for older people in Dutch primary care.

Methods design
individual patient data (IPD) meta-analysis of eight clinically controlled trials.

Setting
primary care sector.

Interventions
combination of (i) identification of older people with complex problems by means of screening, followed by (ii) a multidisciplinary integrated care programme for those identified.

Main outcome
activities of daily living, i.e. a change on modified Katz-15 scale between baseline and 1-year follow-up.

Secondary outcomes
quality of life (visual analogue scale 0–10), psychological (mental well-being scale Short Form Health Survey (SF)-36) and social well-being (single item, SF-36), quality-adjusted life years (Euroqol-5dimensions-3level (EQ-5D-3L)), healthcare utilisation and cost-effectiveness.

Analysis
intention-to-treat analysis, two-stage IPD and subgroup analysis based on patient and intervention characteristics.

Results
included were 8,678 participants: median age of 80.5 (interquartile range 75.3; 85.7) years; 5,496 (63.3%) women. On the modified Katz-15 scale, the pooled difference in change between the intervention and control group was −0.01 (95% confidence interval −0.10 to 0.08). No significant differences were found in the other patient outcomes or subgroup analyses. Compared to usual care, the probability of the intervention group to be cost-effective was less than 5%.

Conclusion
compared to usual care at 1-year follow-up, strategies for identification of frail older people in primary care combined with a proactive integrated care intervention are probably not (cost-) effective.
Knotty: efficient and accurate prediction of complex RNA pseudoknot structures
Authors: Jabbari Hosna , Wark Ian , Montemagno Carlo , Will Sebastian 
Published: May 2018

Abstract

Motivation
The computational prediction of RNA secondary structure by free energy minimization has become an important tool in RNA research. However in practice, energy minimization is mostly limited to pseudoknot-free structures or rather simple pseudoknots, not covering many biologically important structures such as kissing hairpins. Algorithms capable of predicting sufficiently complex pseudoknots (for sequences of length n) used to have extreme complexities, e.g. Pknots has O(n6) time and O(n4) space complexity. The algorithm CCJ dramatically improves the asymptotic run time for predicting complex pseudoknots (handling almost all relevant pseudoknots, while being slightly less general than Pknots), but this came at the cost of large constant factors in space and time, which strongly limited its practical application (∼200 bases already require 256 GB space).

Results
We present a CCJ-type algorithm, Knotty, that handles the same comprehensive pseudoknot class of structures as CCJ with improved space complexity of Θ(n3+Z)—due to the applied technique of sparsification, the number of ‘candidates’, Z, appears to grow significantly slower than n4 on our benchmark set (which include pseudoknotted RNAs up to 400 nt). In terms of run time over this benchmark, Knotty clearly outperforms Pknots and the original CCJ implementation, CCJ 1.0; Knotty’s space consumption fundamentally improves over CCJ 1.0, being on a par with the space-economic Pknots. By comparing to CCJ 2.0, our unsparsified Knotty variant, we demonstrate the isolated effect of sparsification. Moreover, Knotty employs the state-of-the-art energy model of ‘HotKnots DP09’, which results in superior prediction accuracy over Pknots.

Availability and implementation
Our software is available at https://github.com/HosnaJabbari/Knotty.

Supplementary information
Supplementary data are available at Bioinformatics online.
The national cost of adverse drug events resulting from inappropriate medication-related alert overrides in the United States
Authors: Slight Sarah P , Seger Diane L , Franz Calvin , Wong Adrian , Bates David W 
Published: May 2018

Abstract

Objective
To estimate the national cost of ADEs resulting from inappropriate medication-related alert overrides in the U.S. inpatient setting.

Materials and Methods
We used three different regression models (Basic, Model 1, Model 2) with model inputs taken from the medical literature. A random sample of 40 990 adult inpatients at the Brigham and Women’s Hospital (BWH) in Boston with a total of 1 639 294 medication orders was taken. We extrapolated BWH medication orders using 2014 National Inpatient Sample (NIS) data.

Results
Using three regression models, we estimated that 29.7 million adult inpatient discharges in 2014 resulted in between 1.02 billion and 1.07 billion medication orders, which in turn generated between 75.1 million and 78.8 million medication alerts, respectively. Taking the basic model (78.8 million), we estimated that 5.5 million medication-related alerts might have been inappropriately overridden, resulting in approximately 196 600 ADEs nationally. This was projected to cost between $871 million and $1.8 billion for treating preventable ADEs. We also estimated that clinicians and pharmacists would have jointly spent 175 000 hours responding to 78.8 million alerts with an opportunity cost of $16.9 million.

Discussion and Conclusion
These data suggest that further optimization of hospitals computerized provider order entry systems and their associated clinical decision support is needed and would result in substantial savings. We have erred on the side of caution in developing this range, taking two conservative cost estimates for a preventable ADE that did not include malpractice or litigation costs, or costs of injuries to patients.
Relationship of coronary artery calcification with renal function decline and mortality in predialysis chronic kidney disease patients
Authors: Lamarche Michelle C , Hopman Wilma M , Garland Jocelyn S , White Christine A , Holden Rachel M 
Published: May 2018

Abstract

Background
Patients with chronic kidney disease (CKD) have higher levels of coronary artery calcification (CAC) compared with the general population. The role of CAC in renal function decline is not well understood.

Methods
In this prospective cohort study of Stages 3–5 CKD patients with CAC scores kidney function decline, development of end-stage kidney disease (ESKD) and all-cause mortality were determined at 5 and 10 years. Baseline variables included markers of CKD and chronic kidney disease mineral and bone disorder (CKD-MBD), demographics and comorbidities. Multivariable analyses identified predictors of outcomes, and survival curves demonstrated the association of CAC score with ESKD and mortality.

Results
One hundred and seventy-eight patients were enrolled between 2005 and 2007. Independent predictors of ESKD at 5 years were estimated glomerular filtration rate (eGFR) and urine albumin–creatinine ratio (UACR); at 10 years, eGFR was no longer a predictor, but CAC was now significant. Those who developed ESKD at the fastest rate either had the highest CAC score (≥400 AU) or were youngest and had the lowest calcidiol, and highest serum phosphate, UACR and percentage change in CAC per year. Predictors of eGFR decline over 5 years were UACR, parathyroid hormone and CAC score. Predictors of mortality at 5 years were age, diabetes and eGFR and at 10 years also included CAC score.

Conclusions
In Stages 3–5 CKD patients, CAC is an independent predictor of both ESKD and mortality at 10 years. Those who developed ESKD at the fastest rate either had the highest CAC score or the worst CKD-MBD derangements.
Ancient Skepticism
Authors: Bett Richard 
Published: May 2018

While ideas that can loosely be called skeptical may be found from very early in Greek philosophy, skepticism as an organized method of thinking in Greco-Roman antiquity appears in the post-Aristotelian period. There are two distinct traditions or movements of skeptical thought: Pyrrhonian and Academic. The hallmark of ancient Greco-Roman skepticism, in both traditions, is suspension of judgement, brought about by the juxtaposition of equally persuasive opposing views on any given question. In the Pyrrhonist version, but not the Academic, this is claimed to have a practical benefit: ataraxia or tranquility. In both traditions, however, skepticism is understood not merely as a topic of theoretical reflection, but as something to be lived. The Pyrrhonian tradition claimed inspiration from Pyrrho of Elis (c. 360–270 bce), who is usually considered the first Greek skeptic. However, the exact nature of Pyrrho’s thinking is very hard to reconstruct, given the scarcity of the evidence. Pyrrho’s direct influence seems to have been short-lived. But shortly after Pyrrho another skeptical movement arose in the Academy, the school founded by Plato. The first head of the Academy to take the school in a skeptical direction was Arcesilaus of Pitane (316/5–241/0 bce). Whether Pyrrho was an influence on him is a disputed question. But some aspects of Socrates’ activity, as Plato portrays him, might seem to encourage skepticism, and Arcesilaus is said to have acknowledged this influence. The skeptical Academy lasted for roughly two centuries, its other major figure being Carneades of Cyrene (214–129/8 bce). By the early 1st century bce the skepticism of the Academy seems to have moderated considerably, and it was at this point that the Academy itself, as an institution, came to an end. But in reaction to this softening of the skeptical attitude came a new skeptical movement led by Aenesidemus of Cnossos (dates uncertain, but active in the early first century bce), repudiating the Academy and instead identifying itself with Pyrrho. This later Pyrrhonian movement continued for roughly three centuries. We know the names of a few Pyrrhonists. But the only complete Pyrrhonist works we have are the extensive surviving writings of Sextus Empiricus (probably late 2nd or early 3rd century ce). Because Oxford Bibliographies for Pyrrho of Elis and The Academy already exist, this bibliography is somewhat weighted toward the later Pyrrhonist tradition stemming from Aenesidemus.
Modelism and mathematical doxology
Authors: Button Tim , Walsh Sean 
Published: May 2018

AbstractThis chapter outlines a certain attitude to model theory called ‘modelism’. The modelist idea is that structure-talk, as used informally by mathematicians, is to be understood in terms of isomorphism, in the model theorist's sense. For example, modelists will want to explicate talk of ‘the natural numbers' in terms of a particular isomorphism type. As such, modelists face an important doxological question: ‘How can we pick out particular isomorphism types?’ This chapter examines various versions of this question, and in particular what it means to say that it is a doxological question. We also distinguish between objectual and conceptual versions of this question, and show how they relate to Shapiro’s and Hellman’s different versions of structuralism.