bluuebunny/crossref_metadata_2025 huggingface dataset:
Connectivity Map-based discovery of parbendazole reveals targetable human osteogenic pathway
Authors: Brum Andrea M. , van de Peppel Jeroen , van der Leije Cindy S. , Schreuders-Koedam Marijke , Eijken Marco , van der Eerden Bram C. J. , van Leeuwen Johannes P. T. M.
Published: September 2015

Significance

Osteoporosis, a disease characterized by increased bone fragility and fracture risk, affects over 20% of the ever-growing elderly population. It is important to further our knowledge of bone cell biology so we can develop new bone anabolic treatments. By combining genomic and bioinformatic tools against the backdrop of osteogenic differentiating human mesenchymal stromal cells, we have identified a previously unidentified bone anabolic compound that induces osteoblast differentiation in a subset of the hMSC population through cytoskeletal changes and increased bone morphogenetic protein 2 activity. Through this novel approach we identified an important mechanism of lineage allocation and demonstrated the significance of cytoskeletal organization in osteogenic differentiation, providing us with a novel mechanism for bone formation to target for new osteoporosis treatments.
Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of target protein is crucial for the cofactor activity of RCA proteins
Authors: Gautam Avneesh Kumar , Panse Yogesh , Ghosh Payel , Reza Malik Johid , Mullick Jayati , Sahu Arvind
Published: September 2015

Significance

The complement system discriminates self from nonself targets solely owing to the presence of complement regulators on the host cells, which primarily belong to the regulators of complement activation (RCA) protein family. These regulators control complement activation on the host cell surface by two mechanisms termed “cofactor activity” (CFA) and “decay-accelerating activity.” Here, we have identified the critical structural determinants of an RCA protein responsible for imparting the CFA and show that these determinants bridge MG2 (macroglobulin-2) and CUB (complement C1r-C1s, Uegf, Bmp1) domains of C3b and interact with factor I. As a proof of principle, we show that incorporation of putative membrane cofactor protein (CD46) regions responsible for the bridging and factor I interaction in decay acceleration factor (CD55) results in gain of function. We, thus, define the molecular events that govern CFA.
Discriminating direct and indirect connectivities in biological networks
Authors: Kang Taek , Moore Richard , Li Yi , Sontag Eduardo , Bleris Leonidas
Published: September 2015

Significance

We used a combination of computational and theoretical approaches coupled to synthetic biology experimentation in mammalian cells to study direct and indirect connectivities in biological networks. After subjecting benchmark circuits to a range of perturbations, we recovered the edge weights using nonparametric single-cell data resampling coupled with modular response analysis. We discovered that inferred weights of specific network edges undergo divergent shifts under differential perturbations, and that the particular behavior is topology dependent. Incorporating this insight in the analysis of high-throughput experiments may provide a sought-after solution to a longstanding reverse engineering problem.
SPARC triggers a cell-autonomous program of synapse elimination
Authors: López-Murcia Francisco J. , Terni Beatrice , Llobet Artur
Published: September 2015

Significance

Neuronal circuits require eliminating the excess of synaptic connectivity to acquire complete functionality. Here we show that secreted protein acidic and rich in cysteine (SPARC), a molecule secreted exclusively by glia, is a trigger for synapse elimination. Acting through a region located in its C-terminal domain, SPARC activates synapse disassembly and formation of retracted axon terminals in cholinergic neurons in vitro. The onset of this cell-autonomous program in the tails of living tadpoles drives a loss of motor innervation, causing transient paralysis. We propose that along with their well-established role in ending the process of synapse elimination by engulfing retracted terminals, glia can also act as a trigger through the release of specific molecules, such as SPARC.
Structural and evolutionary relationships of “AT-less” type I polyketide synthase ketosynthases
Authors: Lohman Jeremy R. , Ma Ming , Osipiuk Jerzy , Nocek Boguslaw , Kim Youngchang , Chang Changsoo , Cuff Marianne , Mack Jamey , Bigelow Lance , Li Hui , Endres Michael , Babnigg Gyorgy , Joachimiak Andrzej , Phillips George N. , Shen Ben
Published: September 2015

Significance

There are many differences in the sequences of ketosynthase (KS) domains from the well-studied type I polyketide synthases (PKSs) and the more recently discovered acyltransferase (AT)-less type I PKSs. The AT-less type I PKSs generate polyketides with a high degree of structural diversity, which stems from their evolution by horizontal gene transfer. In comparison, canonical type I PKSs evolve by gene duplication. The seven structures of AT-less type I PKS KSs reveal the molecular details surrounding the evolution of substrate specificity and structural diversity, and their overall differences with canonical type I PKS KSs. Understanding the mechanism of substrate specificity will allow reprogramming of the KS active sites to generate polyketide analogues by PKS and polyketide biosynthetic pathway engineering.
Western academic discourse on the post-Soviet de facto state phenomenon
Authors: Yemelianova Galina M.
Published: September 2015

This article examines how the so-called post-Soviet de facto states are conceptualized and discussed within the wider context of Western English-language social and political sciences, including inter-disciplinary Russian, Slavonic, East European and Eurasian area studies. It outlines the main theoretical models and methodologies utilized in the analysis of this phenomenon, and identifies their respective benefits and shortcomings. The article posits that there is considerable unevenness between various theoretical paradigms in terms of their explanatory clarity and their relationship with empirical reality. I argue that Western academic discourse on the post-Soviet de facto states, and on post-Soviet politics more generally, has been increasingly shaped by mono-theoretical determinist models with heavy reliance on deductive quantitative research methods and secondary sources in English language and non-academic analytical reports. A corollary has been a considerable deterioration in the epistemological quality of the discourse on de facto states, and on occasion its politicization.
Reveal Digital: an open access model empowering libraries to become publishers
Authors: GLAHN Peggy
Published: September 2015

Key points

Digitizing cultural heritage, humanities, content is currently being undertaken with institutional or government support but there are opportunities for greater library collaboration.

Using a crowdfunding model to support the creation of digitized collections empowers librarians but also challenges them to think like investors and publishers.

The described model creates an open access collection for the benefit of all scholars and also provides additional benefits for the participating libraries.
The BMJ online: lessons from a 20‐year digital presence
Authors: PAYNE David
Published: September 2015

Key points

The current BMJ is a far cry from the 1995 ‘brochureware’ site.

Journals need to be flexible in their delivery mechanisms to meet user needs.

Online publishing provides an opportunity to extend the target readership.

Responding to user demands to be balanced against proactive development.

Not everything works, but it is better to be innovating than overly cautious.
How to do (or not to do) … translation of national health accounts data to evidence for policy making in a low resourced setting
Authors: Price Jennifer A , Guinness Lorna , Irava Wayne , Khan Idrish , Asante Augustine , Wiseman Virginia
Published: September 2015

For more than a decade, the Organization for Economic Co-operation and Development (OECD), the World Health Organization (WHO) and the World Bank have promoted the international standardization of National Health Accounts (NHA) for reporting global statistics on public, private and donor health expenditure and improve the quality of evidence-based decision-making at country level. A 2010–2012 World Bank review of NHA activity in 50 countries found structural and technical constraints (rather than cost) were key impediments to institutionalizing NHA in many low- and middle-income countries (LMICs). Pilot projects focused resources on data production, neglecting longer-term capacity building for analysing the data, developing ownership among local stakeholders and establishing routine production, utilization and dissemination of NHA data. Hence, genuine institutionalization of NHA in most LMICs has been slow to materialize. International manuals focus on the production of NHA data and do not include practical, incremental and low-cost strategies to guide countries in translating the data into evidence for policy-making. The main aim of this article is to recommend strategies for bridging this divide between production and utilization of NHA data in low-resource settings. The article begins by discussing the origins and purpose of NHA, including factors currently undermining their uptake. The focus then turns to the development and application of strategies to assist LMICs in ‘unlocking’ the hidden value of their NHA. The article draws on the example of Fiji, a country currently attempting to integrate their NHA data into policy formulation, despite minimal resources, training and familiarity with economic analysis of health systems. Simple, low cost recommendations such as embedding health finance indicators in planning documents, a user-friendly NHA guide for evaluating local health priorities, and sharing NHA data for collaborative research have helped translate NHA from raw data to evidence for policymaking.
Diogenes Laertius
Authors: Dorandi Tiziano
Published: September 2015

Diogenes Laertius (3rd century ce) is the author of a collection of poems entitled Pammetros and of a work in ten books known as the Lives and Opinions of Eminent Philosophers. The Lives were dedicated to a woman who was an enthusiastic Platonist (Book 3, § 47 and Book 10, § 29) and whose identity is unknown. Diogenes’ collection of poems in different meters has been for the most part lost; single poems that originally belonged to Diogenes’ Pammetros were later inserted into the narrative structure of the Lives by Diogenes himself. Diogenes’ Lives, however, have survived almost intact, with the exception of the final part of Book 7. The Lives are structured as follows: the prologue (Book 1, §§ 1–21) describes the origins of philosophy; the distinction between sages and philosophers; the succession of the philosophical schools and their separation into two main branches, Ionian philosophy and Italic philosophy; and the division of philosophy into three parts—physics, ethics, and dialectics—and ten principal philosophical schools. The books’ subjects are divided into Book 1: the sages; Book 2: the Ionic school of Anaximander, Anaximenes, Anaxagoras, Socrates, and the Socratics; Book 3: Plato; Book 4: Plato’s successors in the Academy, from Speusippus to Clitomachus; Book 5: Aristotle, Theophrastus, and their successors through Demetrius of Phaleron, including Heraclides of Pontus; Book 6: Antisthenes, Diogenes, and the Cynics; Book 7: Zeno and the Stoics (the surviving text covers as far as Chrysippus, but we presume it originally included philosophers through the time of the 1st-century-ce Roman Stoic Cornutus); Book 8: the Italic school, which includes Pythagoras and the Pythagoreans, Empedocles, and Eudoxus; Book 9: the so-called sporadic philosophers (Heraclitus and Xenophanes), Parmenides, Democritus, Protagoras, Pyrrho, and Timon; and Book 10: Epicurus. Diogenes’ Lives can be considered the earliest history of Greek philosophy to have come down to us, constituting a valuable source of information about the lives and doctrines of the major representatives of ancient philosophical schools up to the 1st century ce.
Michael Dummett
Authors: Weiss Bernhard
Published: September 2015

Born in 1925, Professor Sir Michael Dummett spent most of his career working at the University of Oxford, becoming the Wykeham Professor of Logic there in 1979, a post that he held until his retirement in 1992. He was knighted in 1999 and died in 2011. His work in philosophy is marked by his voluminous study of Frege, a study that runs to five books and spans twenty years. Through his detailed engagement with Frege’s works, Dummett develops a number of his own contributions to the subject. He finds in Frege’s writings a distinctive view of the nature of analytical philosophy, which he embraces as the proper method for philosophy; a conception of the relation between a theory of understanding and that of reference; and a set of commitments that Dummett sees as being distinctively realist. With the publication of “Truth” in 1959, Dummett drew the attention of academic philosophers by advancing a conception of debates about realism as semantic disputes, that is, disputes about the relation of language to the world. The conception was refined and amplified through numerous works over the next forty years. Conceiving of the various realism debates as having an essential underlying commonality allowed Dummett to evince a general opposition to realism, which he calls anti-realism, and which, though owing much to the Fregean conception of the relation of the theory of understanding to that of reference, imports Wittgensteinian lessons to impose constraints on an adequate theory of understanding. Though this article concentrates exclusively on Dummett’s work in philosophy, Dummett also made contributions to social choice theory, the history of card games, writing style, and religion.
Closeness Counts: Increasing Precision and Reducing Errors in Mass Election Predictions
Authors: Quek Kai , Sances Michael W.
Published: September 2015

Mass election predictions are increasingly used by election forecasters and public opinion scholars. While they are potentially powerful tools for answering a variety of social science questions, existing measures are limited in that they ask about victors rather than voteshares. We show that asking survey respondents to predict voteshares is a viable and superior alternative to asking them to predict winners. After showing respondents can make sensible quantitative predictions, we demonstrate how traditional qualitative forecasts lead to mistaken inferences. In particular, qualitative predictions vastly overstate the degree of partisan bias in election forecasts, and lead to wrong conclusions regarding how political knowledge exacerbates this bias. We also show how election predictions can aid in the use of elections as natural experiments, using the effect of the 2012 election on partisan economic perceptions as an example. Our results have implications for multiple constituencies, from methodologists and pollsters to political scientists and interdisciplinary scholars of collective intelligence.
MgtE FromRhizobium leguminosarumIs a Mg2+Channel Essential for Growth at Low pH and N2Fixation on Specific Plants
Authors: Hood Graham , Karunakaran Ramakrishnan , Downie J. Allan , Poole Philip
Published: September 2015

MgtE is predicted to be a Rhizobium leguminosarum channel and is essential for growth when both Mg2+is limiting and the pH is low. N2was only fixed at 8% of the rate of wild type when the crop legume Pisum sativum was inoculated with an mgtE mutant of R. leguminosarum and, although bacteroids were present, they were few in number and not fully developed. R. leguminosarum MgtE was also essential for N2fixation on the native legume Vicia hirsuta but not when in symbiosis with Vicia faba. The importance of MgtE and the relevance of the contrasting phenotypes is discussed.
Optimizing Chemically Induced Resistance in Tomato Against Botrytis cinerea
Authors: Luna Estrella , Beardon Emily , Ravnskov Sabine , Scholes Julie , Ton Jurriaan
Published: September 2015

Resistance-inducing chemicals can offer broad-spectrum disease protection in crops, but can also affect plant growth and interactions with plant-beneficial microbes. We have evaluated different application methods of β-aminobutyric acid (BABA) and jasmonic acid (JA) for long-lasting induced resistance in tomato against Botrytis cinerea. In addition, we have studied nontarget effects on plant growth and root colonization by arbuscular mycorrhizal fungi (AMF). Germinating seeds for 1 week in BABA- or JA-containing solutions promoted seed germination efficiency, did not affect plant growth, and induced resistance in 4-week-old plants. When formulating BABA and JA in carboxymethyl cellulose seed coating, only BABA was able to induce resistance in 4-week-old plants. Root treatment of 1-week-old seedlings with BABA or JA also induced resistance in 4-week-old plants. However, this seedling treatment repressed plant growth at higher concentrations of the chemicals, which was particularly pronounced in hydroponically grown plants after BABA treatment. Both seed coating with BABA, and seedling treatments with BABA or JA, did not affect AMF root colonization in soil-grown tomato. Our study has identified commercially feasible application methods of BABA and JA, which induce durable disease resistance in tomato without concurrent impacts on plant growth or colonization by plant-beneficial AMF.
Bivalved Versus Circumferential Cast Immobilization for Displaced Forearm Fractures: A Randomized Clinical Trial to Assess Efficacy and Safety
Authors: Bae Donald S. , Valim Clarissa , Connell Patricia , Brustowicz Katherine A. , Waters Peter M.
Published: September 2015

Background:

The purpose of this study was to determine the effects of bivalved versus circumferential cast immobilization on maintenance of reduction and associated complications after closed reduction (CR) of radius and/or ulna fractures in children.

Methods:

Two hundred two children with displaced radius and/or ulna fractures were randomized to either circumferential (n=101) or bivalved (n=101) long-arm casts after CR. The mean age was 10±3 years. There were no significant differences between groups in terms of age, sex, or initial fracture displacement or angulation. Clinical and radiographic evaluations were performed at 1, 2, 4, and 6 weeks postreduction. Radiographic loss of reduction (LOR), need for remanipulation or surgery, and associated complications of compartment syndrome, cast saw injury, and neurovascular compromise were recorded.

Results:

Overall, the median angulation of the radius and ulna fractures improved from 20 and 18 degrees to 3 and 2 degrees after CR, respectively. The median cast index after reduction was 0.78 in the bivalved group and 0.80 in the circumferential group. The median angulation of the radius and ulna was 8 and 1 degrees at 4 weeks, with no significant difference between groups. By the fourth week of follow-up, 70 patients (34%)—35 bivalved and 35 circumferential—had radiographic LOR. Forty-seven patients (23%)—23 bivalved and 24 circumferential—underwent remanipulation or surgical reduction and fixation. There were no significant differences between groups with respect to LOR rate or need for surgical treatment. One bivalved patient sustained a cast saw injury, and 3 bivalved patients had transient neurological abnormalities. No patients developed compartment syndrome.

Conclusions:

Cast immobilization is effective in the majority of patients after CR of displaced forearm fractures. There were no significant differences in maintenance of reduction, need for surgery, or complications between bivalved or circumferential long-arm casts.

Level of Evidence:

Level I—therapeutic.
Spontaneous Fatal Intraoperative Rupture of Great Vessel During Growing Rod Lengthening: Do Children With Ehlers-Danlos Syndrome Require the Availability of Vascular Expertise? A Case Report and Review of the Literature
Authors: Working Zachary M. , Hsiao Mark , Sanders John C. , Bratton Susan L. , D’Astous Jacques L.
Published: September 2015

Background:

Ehlers-Danlos syndrome (EDS) is a family of inherited connective tissue diseases. Kyphoscoliotic EDS (kEDS) is associated with severe and early spinal deformity. Very little has been reported regarding the orthopaedic surgical care of kEDS likely due to its rare incidence. A more common subtype is the vascular-type EDS (vEDS, previously labeled type IV), which is associated with reports of vascular complications in the literature.

Methods:

The case report of a single, fatal complication of spontaneous rupture of the superior vena cava, after extubation, subsequent to revision minimal growing rod lengthening in a child with kEDS. We additionally review prior reported cases of kEDS for pediatric spine surgery and the sentinel event of spontaneous vascular rupture in all EDS patients.

Results:

The anterior thoracoabdominal approach in children with kEDS has been associated with severe intravascular complications, with no deaths reported to date. Posterior spinal procedures were associated with frequent overall complications, but no events of perioperative or spontaneous vascular injury were identified before our case.

Reports of spontaneous vessel rupture (n=39) appear more frequently in vEDS, but have been documented in patients with EDS type I (classic EDS or cEDS) and kEDS disease. The 30-day mortality in these patients was 59%. The majority of the deaths occurred on the day of the vascular event. Surviving patients overwhelmingly received intraoperative consultation and treatment from either general or vascular surgeons at their respective institutions for assistance.

Conclusions:

Providers should consider their proximity to available emergent consultation before operating on patients with EDS of any subtype.

Level of Evidence:

Level V—expert opinion.
Successful Pavlik Harness Treatment for Developmental Dysplasia of the Hip and Normal X-Ray at the Age of 2 Years: Is a Longer Follow-up Necessary?
Authors: Allington Nanni J.
Published: September 2015

Background:

Management of developmental dysplasia of the hip (DDH) with a Pavlik harness is a well-known treatment.

Follow-up until skeletal maturity is recommended as long-term studies mention late sequelae.The purpose of this study was to determine whether such a follow-up is necessary in patients treated successfully under a strict protocol.

Methods:

A retrospective review of a consecutive series of normal infants treated for DDH between January 1995 and July 2004 was undertaken.

Only normal infants with frankly pathologic hips treated successfully with a Pavlik harness were included, and with a normal anteroposterior (AP) pelvis x-ray at the age of 2 years.

All infants with any type of neurological disease, syndrome, other form of treatment for DDH, and failure of the Pavlik harness were excluded.

At the last follow-up, a clinical examination and a standing AP pelvis x-ray were performed.

Results:

A total of 109 hips in 83 children were available for review. The mean follow-up was of 10 years and 2 months. All 109 hips had a normal clinical examination and a normal AP pelvis x-ray: a mean center-edge angle (CEA) of 29.5 degrees, SD±4.1 degrees, a mean acetabular index (AI) of 1457±3.74 degrees, a mean Sharp’s angle of 41.92±3.42 degrees, a Seringe-Severin score of IA, a normal teardrop figure, no signs of avascular necrosis, and Moses circles <2.

Conclusion:

This study strongly suggests that in a selected group of patients treated for DDH with a Pavlik harness, under a strict protocol, and a normal x-ray at 2 years of age, a long-term follow-up is not necessary.

Level of Evidence:

Level III—therapeutic.
Candidate Loci are Revealed by an Initial Genome-wide Association Study of Juvenile Osteochondritis Dissecans
Authors: Yellin Joseph L. , Trocle Ashley , Grant Struan F.A. , Hakonarson Hakon , Shea Kevin G. , Ganley Theodore J.
Published: September 2015

Background:

Osteochondritis dissecans (OCD) is a condition that oftentimes causes significant knee pain in pediatric patient populations. If left untreated, OCD significantly increases the risk of developing degenerative osteoarthritis along with its associated consequences and costs. Although a genetic component has been suggested to play a role in this disorder, few studies have been carried out in order to determine the underlying genetic etiology of this relatively common complex trait. The goal of our study was to perform an initial genome-wide association study (GWAS) to uncover candidate loci associated with the pathogenesis of OCD.

Methods:

Blood samples were acquired from 2 cohorts, aged 0 to 18 years old, consisting of 209 OCD cases and 1855 population-matched controls. Agencourt Genfind DNA isolation technology was used to isolate high-quality DNA from each sample. Genotype data was then generated utilizing the Illumina Infinium BeadChip array to examine single-nucleotide polymorphisms (SNPs).

Results:

In an initial GWAS analysis of our cohort, where a SNP was excluded if the Hardy-Weinberg Equilibrium test P<0.0001, the minor allele frequency<5%, and the genotyping call rate<90%, we obtained our first results for OCD. Although there was no SNP strictly reaching the threshold for genome-wide significance at this early stage, multiple SNPs (35) at several loci revealed evidence of suggestive association with OCD (P<5.0×10−5).

Conclusions:

The results from our preliminary study are encouraging. Herein we not only discuss the relevance and applicability of GWAS in studying a genetic basis for OCD, but have also identified top signals that may suggest loci involved in coordinated expression as well as a transcription factor involved in development that may be highly relevant to this trait.

Clinical Relevance:

If genetic predispositions for OCD are detected early enough in life, attempts at activity modification, counseling, and orthopaedic monitoring may successfully reduce progression of this condition, which may lead to progressive osteoarthritis in the third to fourth decade in at-risk patients.
Profile and Determinants of Neurocognitive Dysfunction in a Sample of Adult Nigerians With Heart Failure
Authors: Adebayo Philip Babatunde , Akintunde Adeseye Abiodun , Audu Morenike Bosede , Ayodele Olugbenga Edward , Akinyemi Rufus Olushola , Opadijo Oladimeji George
Published: September 2015

Background:

Heart failure (HF) in Africans is peculiar because subjects are younger than whites and have lower socioeconomic and educational level in addition to the high prevalence of hypertension-related etiology and increased mortality. Whereas cognitive dysfunction have been demonstrated among whites with HF, the prevalence and pattern of cognitive dysfunction among sub-Saharan African patients with HF have not been evaluated against this background.

Objectives:

The aim of this study is to determine the 1-year prevalence and the factors contributing to cognitive dysfunction in a cohort of Nigerian patients with HF.

Materials and Methods:

In this cross-sectional case-control study, cognitive performance was evaluated in 111 consecutive individuals (60 HF patients and 51 controls matched for age, gender, and level of education) using the Community Screening Interview for Dementia, Word List Learning Delayed Recall, Boston Naming Test, and Modified Token Test. Other clinical and disease-specific variables were collated and correlated with cognitive performance.

Results:

The mean total Community Screening Interview for Dementia, Word List Learning Delayed Recall, Boston Naming Test, and Modified Token Test scores were significantly lower among HF patients (P = < .001). The prevalence of global cognitive dysfunction was 90.0% in HF and 5.9% among controls (odds ratio, 15.3; 95% confidence interval, 5.08–46.01). Elevated systolic blood pressure, increased comorbidity index, and wide pulse pressure were significantly associated with poorer performance on at least 1 neuropsychological test. Using a multivariate linear regression analysis, pulse pressure retained its significance (P = .029; 95% confidence interval, −0.117 to −0.007) as the most important predictor of cognitive dysfunction in the cohort of HF patients.

Conclusion:

Cognitive dysfunction is prevalent among this sample of Nigerians with HF. Regular cognitive screening is therefore advocated among this high-risk group. Controlling comorbidities as well as blood pressure may improve cognitive performance among patients with HF.
Falls in Patients With Heart Failure
Authors: Lee Kayoung , Pressler Susan J. , Titler Marita
Published: September 2015

Background:

Many heart failure patients show fall-related signs/symptoms including postural hypotension, cerebellar injury, and cognitive impairments. Falls contribute to injuries, increased healthcare use, and death, but falls have been understudied in this population.

Objective:

The purpose of this review is to identify fall rates, fall injuries, and risk factors for falls in heart failure patients.

Methods:

A systematic literature review was conducted using MEDLINE, CINAHL, PubMed, PsycINFO, and Cochrane Library to identify publications from August 1973 to June 2013. Keywords were accidental falls, heart failure, fall rates, fall injuries, and fall risk. Inclusion criteria were publications that were primary data based, included heart failure sample, had falls/fall risk as study variables, and were written in English language. Exclusion criteria were quality improvement/evaluation, case reports/studies, news, opinions, narrative reviews, meeting reports, reflections, and letters to editors. Data were abstracted using a standardized data collection form.

Results:

Four publications met the inclusion criteria. In the first study, fall rate was 43%, which is higher than the fall rates among community-dwelling older adults. Fall-related injuries were not examined in any of studies. Benzodiazepines and digoxin were identified as medications that increased risk of falls in 1 case-control study. Loop diuretics were not significantly associated with falls in 1 cohort study. In the fourth study, patients who had poor gait and balance were at greater risk of falling.

Conclusions:

Future studies are needed to determine factors associated with falls, characterize injuries resulting from falls, and most importantly design testable interventions to prevent falls in heart failure patients.
A Ventricular Assist Device Recipient and Suicidality
Authors: Balliet Wendy E. , Madan Alok , Craig Michael L. , Serber Eva R. , Borckardt Jeffery J. , Pelic Christine , Barth Kelly , Hale Anthony , van Bakel Adrian B. , Peura Jennifer L.
Published: September 2015

Background:

Ventricular assist device (VAD) recipients are at high risk of depression and anxiety, and poor psychosocial functioning is associated with worse medical outcomes.

Purpose:

We present a case of a 31-year-old depressed patient who demonstrated passive suicidal behavior through multiple episodes of noncompliance, including temporarily discontinuing warfarin (Coumadin) several months after VAD implantation. The patient’s psychosocial and medical histories and outcomes are presented.

Conclusions:

This case underscores the importance of pre-VAD as well and ongoing psychosocial evaluation and management for this unique patient population.

Clinical Implications:

Medical teams who are treating patients with cardiovascular disease who are under consideration for VAD or heart transplantation need to be aware of the multitude of ways in which patients can express depressed and suicidal mood and work with a multidisciplinary team to treat such symptoms to optimize patients’ success with VAD/heart transplantation.
Structural symmetry in evolutionary games
Authors: McAvoy Alex , Hauert Christoph
Published: September 2015

In evolutionary game theory, an important measure of a mutant trait (strategy) is its ability to invade and take over an otherwise-monomorphic population. Typically, one quantifies the success of a mutant strategy via the probability that a randomly occurring mutant will fixate in the population. However, in a structured population, this fixation probability may depend on where the mutant arises. Moreover, the fixation probability is just one quantity by which one can measure the success of a mutant; fixation
time
, for instance, is another. We define a notion of homogeneity for evolutionary games that captures what it means for two single-mutant states, i.e. two configurations of a single mutant in an otherwise-monomorphic population, to be ‘evolutionarily equivalent’ in the sense that
all
measures of evolutionary success are the same for both configurations. Using asymmetric games, we argue that the term ‘homogeneous’ should apply to the evolutionary process as a whole rather than to just the population structure. For evolutionary matrix games in graph-structured populations, we give precise conditions under which the resulting process is homogeneous. Finally, we show that asymmetric matrix games can be reduced to symmetric games if the population structure possesses a sufficient degree of symmetry.
Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet
Authors: Pearce D. J. G. , Turner M. S.
Published: September 2015

Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines.
DyNAMiC Workbench: an integrated development environment for dynamic DNA nanotechnology
Authors: Grun Casey , Werfel Justin , Zhang David Yu , Yin Peng
Published: September 2015

Dynamic DNA nanotechnology provides a promising avenue for implementing sophisticated assembly processes, mechanical behaviours, sensing and computation at the nanoscale. However, design of these systems is complex and error-prone, because the need to control the kinetic pathway of a system greatly increases the number of design constraints and possible failure modes for the system. Previous tools have automated some parts of the design workflow, but an integrated solution is lacking. Here, we present software implementing a three ‘tier’ design process: a high-level visual programming language is used to describe systems, a molecular compiler builds a DNA implementation and nucleotide sequences are generated and optimized. Additionally, our software includes tools for analysing and ‘debugging’ the designs
in silico
, and for importing/exporting designs to other commonly used software systems. The software we present is built on many existing pieces of software, but is integrated into a single package—accessible using a Web-based interface at http://molecular-systems.net/workbench. We hope that the deep integration between tools and the flexibility of this design process will lead to better experimental results, fewer experimental design iterations and the development of more complex DNA nanosystems.
Conserved integrals for inviscid compressible fluid flow in Riemannian manifolds
Authors: Anco Stephen C. , Dar Amanullah , Tufail Nazim
Published: September 2015

An explicit determination of all local conservation laws of kinematic type on moving domains and moving surfaces is presented for the Euler equations of inviscid compressible fluid flow in curved Riemannian manifolds in
n
>1 dimensions. All corresponding kinematic constants of motion are also determined, along with all Hamiltonian kinematic symmetries and kinematic Casimirs which arise from the Hamiltonian structure of the inviscid compressible fluid equations.
Evolutionary graph theory revisited: when is an evolutionary process equivalent to the Moran process?
Authors: Pattni Karan , Broom Mark , Rychtář Jan , Silvers Lara J.
Published: September 2015

Evolution in finite populations is often modelled using the classical Moran process. Over the last 10 years, this methodology has been extended to structured populations using evolutionary graph theory. An important question in any such population is whether a rare mutant has a higher or lower chance of fixating (the fixation probability) than the Moran probability, i.e. that from the original Moran model, which represents an unstructured population. As evolutionary graph theory has developed, different ways of considering the interactions between individuals through a graph and an associated matrix of weights have been considered, as have a number of important dynamics. In this paper, we revisit the original paper on evolutionary graph theory in light of these extensions to consider these developments in an integrated way. In particular, we find general criteria for when an evolutionary graph with general weights satisfies the Moran probability for the set of six common evolutionary dynamics.
Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke
Authors: Weissman Irving
Published: September 2015

The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK.
Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells
Authors: Rostovskaya Maria , Bredenkamp Nicholas , Smith Austin
Published: September 2015

Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors byin vitrodifferentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitorsin vitrofrom both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification.
Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic
Authors: Whiting Paul , Kerby Julie , Coffey Peter , da Cruz Lyndon , McKernan Ruth
Published: September 2015

Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic.
Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population
Authors: Robinson Elise B. , St. Pourcain Beate , Anttila Verneri , Kosmicki Jack , Bulik-Sullivan Brendan , Grove Jakob , Maller Julian , Samocha Kaitlin E. , Sanders Stephan , Ripke Stephan , Martin Joanna , Hollegaard Mads V. , Werge Thomas , Hougaard David M. , iPSYCH-SSI-Broad Autism Group  , Neale Benjamin M. , Evans David M. , Skuse David , Bo Mortensen Preben , Børglum Anders D. , Ronald Angelica , Davey Smith George , Daly Mark J.
Published: September 2015

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of that risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortia and population based resources, we find genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both inherited andde novovariation, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in an ASD or other neuropsychiatric disorder diagnosis. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.
Custom AFM for X-ray beamlines:in situbiological investigations under physiological conditions
Authors: Gumí-Audenis B. , Carlà F. , Vitorino M. V. , Panzarella A. , Porcar L. , Boilot M. , Guerber S. , Bernard P. , Rodrigues M. S. , Sanz F. , Giannotti M. I. , Costa L.
Published: September 2015

A fast atomic force microscope (AFM) has been developed that can be installed as a sample holder for grazing-incidence X-ray experiments at solid/gas or solid/liquid interfaces. It allows a wide range of possible investigations, including soft and biological samples under physiological conditions (hydrated specimens). The structural information obtained using the X-rays is combined with the data gathered with the AFM (morphology and mechanical properties), providing a unique characterization of the specimen and its dynamicsin situduring an experiment. In this work, lipid monolayers and bilayers in air or liquid environment have been investigated by means of AFM, both with imaging and force spectroscopy, and X-ray reflectivity. In addition, this combination allows the radiation damage induced by the beam on the sample to be studied, as has been observed on DOPC and DPPC supported lipid bilayers under physiological conditions.
Presentation of spatial information in navigation aids for the visually impaired
Authors: Innala Ahlmark Daniel , Hyyppä Kalevi
Published: September 2015

Purpose

– The purpose of this paper is to present some guidelines on how different means of information presentation can be used when conveying spatial information non-visually. The aim is to further the understanding of the qualities navigation aids for visually impaired individuals should possess.

Design/methodology/approach

– A background in non-visual spatial perception is provided, and existing commercial and non-commercial navigation aids are examined from a user interaction perspective, based on how individuals with a visual impairment perceive and understand space.

Findings

– The discussions on non-visual spatial perception and navigation aids lead to some user interaction design suggestions.

Originality/value

– This paper examines navigation aids from the perspective of non-visual spatial perception. The presented design suggestions can serve as basic guidelines for the design of such solutions.
Co-designing a speech interface for people with dysarthria
Authors: Hamidi Foad , Baljko Melanie , Ecomomopoulos Connie , Livingston Nigel J. , Spalteholz Leonhard G.
Published: September 2015

Purpose

– The purpose of this paper is to describe the development and evaluation of CanSpeak which is an open-source speech interface for users with dysarthria of speech. The interface can be customized by each user to map a small number of words they can speak clearly to commands in the computer system, thereby adding a new modality to their interaction.

Design/methodology/approach

– The interface was developed in two phases: in the first phase, the authors used participatory design to engage the users and their community in the customization of the system, and in the second phase, we used a more focussed co-design methodology during which a user of the system became a co-designer by directly making new design decisions about the system.

Findings

– The study showed that it is important to include assistive technology users and their community in the design and customization of technology. Participation led to increased engagement, adoption and also provided new ideas that were rooted in the experience of the user.

Originality/value

– The co-design phase of the project provided an opportunity for the researchers to work closely with a user of their system and include her in design decisions. The study showed that by employing co-design new insights into the design domain can be revealed and incorporated into the design that might not be revealed otherwise.
EdgeBraille: Braille-based text input for touch devices
Authors: Mattheiss Elke , Regal Georg , Schrammel Johann , Garschall Markus , Tscheligi Manfred
Published: September 2015

Purpose

– The purpose of this paper is to discuss the issue of tailored text input methods for visually impaired and blind users that are needed on touchscreen devices to support their accessibility. Previous approaches still have issues related to the necessity of searching for characters, slow entry speeds or cumbersome handling.

Design/methodology/approach

– The authors developed a new Braille-based text input method named EdgeBraille, which allows entering six-point Braille characters by swiping one finger along the edges of the touchscreen in an arbitrary sequence. The approach was compared with the current standard method of a talking keyboard, first in a short-term lab study (14 participants) and then during two weeks of daily training (seven participants).

Findings

– Overall EdgeBraille was perceived well by the users and possesses favourable handling characteristics. In terms of user performance (words per minute and error rate) the authors found no significant differences between the two methods. However, based on the evaluation results and the feedback of the participants the authors identified possibilities for improvement in terms of a smaller EdgeBraille version allowing the entry of eight-point Braille characters, and conducted a proof-of-concept study (seven participants).

Originality/value

– In the paper the authors comprehensively reflect on advantages and disadvantages of Braille-based methods in general and EdgeBraille in particular. The authors argue why and how Braille-based methods should serve as complement to current text input paradigms based on talking keyboard and indicate future directions of research.