bluuebunny/crossref_metadata_2025 huggingface dataset:
RISK AND RETURNS OF SPRING AND FALL CALVING FOR BEEF CATTLE IN TENNESSEE
Authors: HENRY GAVIN W. , BOYER CHRISTOPHER N. , GRIFFITH ANDREW P. , LARSON JAMES , SMITH AARON , LEWIS KAREN
Published: June 2016

We determined the profitability and risk for spring- and fall-calving beef cows in Tennessee. Simulation models were developed using 19 years of data and considered the seasonality of cattle prices and feed prices for least-cost feed rations to find a distribution of net returns for spring- and fall-calving seasons for two weaning months. Fall calving was more profitable than the spring calving for all feed rations and weaning months. Fall calving was also risk preferred over spring calving for all levels of risk aversion. Higher calf prices at weaning were the primary factor influencing the risk efficiency of fall calving.
Delayed complications and functional outcome of isolated sternal fracture after emergency department discharge: a prospective, multicentre cohort study
Authors: Racine Samuel , Émond Marcel , Audette-Côté Jean-Sébastien , Le Sage Natalie , Guimont Chantal , Moore Lynne , Chauny Jean-Marc , Bergeron Éric , Vanier Laurent
Published: June 2016

Objective

The aim of this study was to determine the incidence of delayed complications, specifically hemothorax, and functional outcome in patients with isolated sternal fracture discharged from the emergency department (ED) compared to patients with other minor thoracic trauma.

Methods

This prospective cohort study was conducted in four university-affiliated Canadian EDs. Patients ages 16 and older discharged from the ED with an isolated minor thoracic injury were included and categorized as isolated sternal fracture, rib fracture, or no fracture. A standardized clinical and radiological follow-up was performed at 7 and 14 days as well as a phone follow-up at 30 and 90 days post-injury. Functional outcome was determined using the Medical Outcome Short-Form Health Survey (SF-12).

Results

A total of 969 patients were included, of whom 32 (3.3%) had an isolated sternal fracture, 304 (31.3%) had rib fracture, and 633 (65.3%) had no fracture. Within 14 days, 112 patients presented with a delayed hemothorax: 12.5% of sternal fracture patients, 23% of rib fracture(s) patients, and 6% of minor thoracic injury patients without fracture (p<0.05). At 90 days, 57.1% of patients with sternal fracture had moderate to severe disability compared to 25.4% and 21.2% for both of the other groups, respectively (p<0.001).

Conclusion

In this prospective study, we found that 12.5% (n=4,p<0.05) of patients with sternal fracture developed a delayed hemothorax, but the clinical significance of this remains questionable. The proportion of patients with sternal fracture who had moderate to severe disability was significantly higher than that of patients with other minor thoracic trauma.
Profile and Management of Musculoskeletal Injuries Associated With the Lushan Earthquake in 2013
Authors: Chen Xuxu , Yang Tianfu , Li Jian
Published: June 2016

On April 20, 2013, a 7.0-magnitude earthquake hit Lushan County, Ya’an City, Sichuan Province in southwest China. West China Hospital of Sichuan University, the largest and best hospital in Sichuan Province, is located in the city of Chengdu—about 100 km from the epicenter—and provided medical treatment to a total of 400 seismic patients. In this article, we retrospectively investigated 199 patients with musculoskeletal injuries who were treated in the Department of Orthopedics. Based on the seismic intensity distribution map, injury-occurring locations were divided into 5 grade-related areas: IX, VIII, VII, VI, and ≤V grade-area. The characteristics of seismic injuries were analyzed according to the geographic distribution of victims. We found that the constituent ratio of injury causes significantly differed in different earthquake areas according to the seismic intensity. (Disaster Med Public Health Preparedness. 2018; 12: 408–410)
New species from Late Cretaceous New Jersey amber and stasis in subfamily Attageninae (Insecta: Coleoptera: Dermestidae)
Authors: Peris David , Háva Jiří
Published: June 2016

A new fossil species of Dermestidae (Insecta: Coleoptera), preserved in Late Cretaceous (Turonian) amber from New Jersey, is described asAttagenus(Aethriostoma)turonianensisn. sp. The specimen is fossilized in translucent amber, but 3D imaging using propagation phase-contrast X-ray synchrotron microtomography allowed detailed classification and description. This species is the oldest representative of the subfamily Attageninae and the third fossil species described in the family from the entire Mesozoic. Dermestidae comprise beetle species that typically feed on carcasses, although some Recent species ofAttagenusLatreille, 1802 are known to feed on plant debris, which is highly abundant in amber deposit sediments. This new species is evidence for diversification in the family during the Early Cretaceous as well as long morphological conservation of diagnostic features of the genusAttagenusfrom the Late Cretaceous. Analyzing the taxa from Mesozoic ambers that show stasis, the small size of the specimens together with a specific ecology could explain the stability of these lineages.
Earliest Evidence of Neolithic Collective Burials from Eastern Iberia: Radiocarbon Dating at the Archaeological Site of Les Llometes (Alicante, Spain)
Authors: Salazar-García Domingo C , García-Puchol Oreto , de Miguel-Ibáñez María Paz , Talamo Sahra
Published: June 2016

In the Valencia region of Spain, the dominant use of natural caves for collective burials during the Late Neolithic and Chalcolithic periods has been documented. Collective burials are central to the hypothesis about social relationships in Copper Age societies from Iberia, and key to interpreting kinship-based societies. Les Llometes (Alcoi, Alicante) is one of the biggest collective burial sites existing in eastern Iberia. This article presents the direct14C dates on 25 skeletal remains at the site. The results indicate that the site was used as a burial place from the end of the 5th millennium cal BC until the end of the 4th millennium cal BC, and is a first milestone for future studies that will shed light on the transition towards social structure through the use of a cemetery space. Moreover, this research is one of the few investigations of Late Neolithic collective burials in Iberia that comprises an extensive accelerator mass spectrometry (AMS)14C data set of almost all the individuals reported at a single site. This case also serves to highlight the utility of revisiting materials from historic excavations by14C dating all the skeletal remains that define the minimum number of individuals, and therefore ensuring a more complete picture of the prehistoric human record.
Morphometric and phylogenetic analyses of Serpentirhabdias viperidicus n. sp. (Nematoda: Rhabdiasidae) from the lancehead snake Bothrops moojeni Hoge, 1966 (Reptilia: Serpentes: Viperidae) in Brazil
Authors: Morais D.H. , Aguiar A. , Müller M.I. , Narciso R.B. , da Silva L.A.F. , da Silva R.J.
Published: June 2016

Serpentirhabdias viperidicus n. sp. (Nematoda: Rhabdiasidae) is described from the lungs of the ‘Brazilian lancehead’ Bothrops moojeni (Hoge, 1966) from the savannah in São Paulo State, Brazil. The new species is the eighth species of Serpentirhabdias described in the Neotropical region, and differs from other species mainly by a combination of characters: lips slightly notable, presence of fine striations at posterior ends, presence of two parallel lines with intercalated pores, a pore-shaped phasmid situated at the level of the anal aperture and another two in the posterior half of the tail. It is the first species of Serpentirhabdias reported in this snake host and the second species of this genus found parasitizing South American viperidian snakes. Molecular phylogenetic analysis using ribosomal (ITS and 28S partial) genes confirms Serpentirhabdias viperidicus n. sp. as a new species that clustered in the Serpentirhabdias clade, sister taxon to Serpentirhabdias fuscovenosa and Serpentirhabdias elaphe. This is the first description of Serpentirhabdias species from Brazil using molecular approaches and morphological characters to confirm the monophyly of this recent genus.
Before the Body Count: Homicide Statistics and Everyday Security in Latin America
Authors: WILLIS GRAHAM DENYER
Published: June 2016

Homicide statistics are a widely accepted metric of security and democracy. This article argues for a focus on how bodies come or do not come to be counted – of what happens before states enumerate. The experience of São Paulo relates that how many people die and how many do not is connected to the governance of an organised crime group known as the PCC. The punishment practices of the PCC and groups like it throughout Latin America reshape the lived paradigm of governance over life and death, albeit in concealed ways. Statistics are produced by and are productive of a de jure state, different from the state de facto. The acceptance of state-made homicide figures, whether for analysis, visualisation or political claims, is consequential for the future of lived security and social science knowledge production.
Women's Voices, Men's Lives: Masculinity in a North Indian Urdu newspaper
Authors: ROBB MEGAN EATON
Published: June 2016

Literary journals and newspapers aiming to reform the religious beliefs and domestic habits of women were common in early twentieth-century North India. Although most readings have focused on how these texts reflected male legislation of women's behaviour, we should look at Muslim reformist literature to understand male experiences; this investigation offers new insights into an emergent middle-class identity defined more by manners than birth. Readings of a previously little-researched Urdu newspaper,Madinah, and its women's section offer new insights on male experiences of reformism, characterized by profound ambivalence. Playfulness emerged in some reformist descriptions of women's voices, channelling the influence ofrekhti. UltimatelyMadinahcultivated pride in Islam's strict division of gender roles and conversely threatened men with shame for failing to regulate uneducated women. Descriptions of powerful, Ottoman women warriors were framed to incite men to acts of bravery, using reports from Europe as cautionary examples of the over-indulgence of women. While the newspaper offered outlets for men to express curiosity about women's experiences, ultimately reformist literature limited expressions of pleasure. Male ambivalence regarding the implications of the reformist project remained embedded in writing about women.
Temporal reproduction and its neuroanatomical correlates in adults with attention deficit hyperactivity disorder and their unaffected first-degree relatives
Authors: Pironti V. A. , Lai M.-C. , Morein-Zamir S. , Müller U. , Bullmore E. T. , Sahakian B. J.
Published: June 2016

Background

Little is known about time perception, its putative role as cognitive endophenotype, and its neuroanatomical underpinnings in adults with attention deficit hyperactivity disorder (ADHD).

Method

Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 typically developing controls matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional grey-matter volumes. Temporal processing was investigated as a putative cognitive endophenotype using a temporal reproduction paradigm. General linear modelling was employed to examine the relationship between temporal reproduction performances and grey-matter volumes.

Results

ADHD participants were impaired in temporal reproduction and unaffected first-degree relatives performed in between their ADHD probands and typically developing controls. Increased grey-matter volume in the cerebellum was associated with poorer temporal reproduction performance.

Conclusions

Adults with ADHD are impaired in time reproduction. Performances of the unaffected first-degree relatives are in between ADHD relatives and controls, suggesting that time reproduction might be a cognitive endophenotype for adult ADHD. The cerebellum is involved in time reproduction and might play a role in driving time performances.
Noise Affects Performance on the Montreal Cognitive Assessment
Authors: Dupuis Kate , Marchuk Veronica , Pichora-Fuller M. Kathleen
Published: June 2016

L’objectif était d’investiguer l’impact de la présence d’un bruit de fond sur la performance au Montreal Cognitive Assessment (MoCA). Deux versions du MoCA ont été administrées, utilisant écouteurs, avec des niveaux bas et élevés de bruit de fond à deux groupes de personnes âgées (un groupe présentant une audition cliniquement normale, le second présentant une perte d’audition) ainsi qu’à un groupe de jeunes adultes. Les niveaux d’intensité utilisés pour présenter la parole et le bruit étaient personnalisés en fonction des habiletés des participants présentant une perte de l’ouïe, et ce en vue de créer un niveau de difficulté uniforme à travers les participants dans la condition de bruit plus élevé. Les deux groupes de personnes âgées ont obtenu des scores plus faibles au MoCA en comparaison aux jeunes adultes. Il est également important de souligner que tous les participants ont obtenu des scores plus faibles au MoCA lorsque le test était administré dans un contexte de bruit élevé (M = 22,7/30), en comparaison à un contexte de bruit faible (M = 25,7/30, p < .001). Ces résultats suggèrent que le bruit de fond présent dans un contexte d’évaluation devrait être pris en considération au moment de l’administration de tests cognitifs ainsi que dans l’interprétation des résultats, en particulier lors de l’essai des adultes plus âgés.
The Concept of Dignity and Its Use in End-of-Life Debates in England and France
Authors: HORN RUTH , KERASIDOU ANGELIKI
Published: June 2016

Dignity is one of the most controversial and yet commonly used terms in debates regarding end-of-life issues. The term “dignity” can take various meanings. For example, it can be used to denote the respect owed to an individual person, or to signify the intrinsic value of humankind as a whole. These two different understandings of dignity inevitably lead to different approaches to end-of-life decisionmaking.

This article explores the meaning of the term “dignity” in two European countries, England and France. Our analysis compares public debates and legislation on end-of-life-related issues in these two countries. We argue that in England dignity is most commonly understood as respect for individual autonomy, whereas in France dignity usually signifies respect for humanity as a whole. We demonstrate that the difference in the conceptualization of the term leads to different ethical, and hence legal and practical, approaches to end-of-life issues and vulnerable patients. Our particular focus is on (1) withdrawing/withholding life-sustaining treatment, (2) respect for patient preferences, and (3) assistance in dying.

Given the difference in the understanding of dignity, and the underlying philosophical approaches, it appears that there is still a long way to go before we can establish common guidelines on end-of-life decisions across Europe and beyond. However, clarifying the use of the term “dignity” in different discussions around Europe could hopefully facilitate this endeavor.
Healthcare in Australia
Authors: DALTON-BROWN SALLY
Published: June 2016

No single issue has dominated health practitioners’ ethical debates in 2014 in Australia, but a controversial decision on gene patenting and the media focus on “Dr. Death,” euthanasia campaigner Dr. Philip Nitschke, have given new life to these two familiar (and global) debates. Currently a dying with dignity bill, drafted by the Australian Green Party, is under examination. The Senate inquiry into the bill received more than 663 submissions, with 57% opposed and 43% in support of the bill, which has now been referred to a Senate committee. Will this be another of Australia’s failed attempts to legalize euthanasia? The trial of Dr. Nitschke begins on November 10, 2014.
Bioethics in Iceland
Authors: ÁRNASON VILHJÁLMUR
Published: June 2016

This article examines ethical issues debated in Iceland concerning population genetic research, specifically methods of collecting biosamples and ways to return clinically relevant results to participants. Also discussed are scientific research in the health sector, a bill on surrogacy, and a policy on consent for organ donation.
Social Responsibility and Healthcare in Finland
Authors: AHOLA-LAUNONEN JOHANNA
Published: June 2016

This article examines current trends and prospects in Finnish healthcare literature and discussion. The Finnish healthcare system was long considered to manifest an equal, universal, and solidaristic welfare scheme. However, recent data reveals structural inequalities in access to healthcare that result in health differences among socioeconomic groups. The political will aims at tackling these inequalities, but the ideological trend toward responsibilization of the individual taking place across political spheres elsewhere in Europe creates potential challenges to this goal. The applications of this trend have a theoretical background in the responsibility-sensitive egalitarian—or luck egalitarian—tradition. The theory, which is unfit for real-life policy applications, has explicit appeal in considerations aiming at the responsibilization of the individual within the healthcare sector. It remains to be seen in which direction the Finnish welfare schemes will continue to develop.
The Social Framework Surrounding the Development of Regenerative Medicine in Japan
Authors: NAKAZAWA EISUKE , TAKIMOTO YOSHIYUKI , AKABAYASHI AKIRA
Published: June 2016

In 2014, the Japanese government amended the laws concerning regenerative medicine. This reform aimed to contribute to the appropriate promotion of regenerative medicine and new drug discovery for intractable diseases using stem cells. It also helped restrict stem cell tourism, that is, provision of stem cell therapy of unclear efficacy and safety to tourists from abroad, and its relaxed regulations may even lead to the resolution of the drug lag problem. Stem cell medicine is positioned as a part of a national growth strategy that requires cooperation among the industry, government, healthcare field, and academia. It can be characterized as a “mesoscopic strategy,” in that it aims to achieve high-level technological developments that would allow results from human-induced pluripotent stem cell and traditional stem cell research to contribute to regenerative medicine and drug development for intractable diseases, while attempting to strike a balance with commercialization and improved access of citizens to cutting-edge medical care.
Conflicts about Conflict of Interest
Authors: KELLY TERRENCE
Published: June 2016

Pharmaceutical representatives use detailing, gift giving, and the donation of free samples as a means to gain access to and influence over physicians. In biomedical ethics, there has been an ongoing debate as to whether these practices constitute an unethical conflict of interest (COI) on the part of the physician. Underlying this debate are the following antecedent questions: (1) what counts as a conflict of interest, (2) when are such conflicts unethical, and (3) how should the ethical physician respond to conflicts? This article distinguishes between two perspectives that have been developed on these issues: a reliable performance model (PM) and a trustworthiness model (TM). PM advocates argue that a conflict of interest can only be established by demonstrating that a particular influence is undermining the reliability of the physician’s judgment, and this requires empirical evidence of negative patient outcomes. TM advocates, on the other hand, argue that because of the fiduciary nature of the patient-physician relationship, physicians have an obligation to develop and be worthy of patient trust. A COI, on this view, is a condition that undermines the warrant for patients to judge a physician as trustworthy. Although there is much that is right in the PM, it is argued that the TM does a better job of responsibly addressing the unique vulnerabilities of the patient. The TM is then applied to the practices of detailing, gift giving, and sample donation. It is concluded that these practices constitute an unethical conflict of interest.
The Case
Authors: MISHRA RUCHIKA
Published: June 2016

Mr. Hope is a 40-year-old man who has resided at a long-term care facility for the past 10 years. The resident was originally admitted to the nursing home for his inability to care for himself secondary to advanced AIDS and complications from progressive multifocal leukoencephalopathy (PML). When he initially arrived at the nursing home, Mr. Hope was able to smile and appeared to respond to some of the staff’s requests. Now, he responds by wincing when told that procedures are being performed and especially when he is told that he has to go back to the hospital. He is extremely contracted, with his arms wedded to his chest in a crossed fashion, as though he is protecting himself from blows. Mr. Hope’s family consists of a partner, his parents, and one sibling. Numerous conversations have been had with the family, and according to the facility staff, “they persist in continuing aggressive measures with the hope that the patient will wake up and walk out of the facility.” What had been frequent visits to the local hospital ER have increased substantially in the last few months, for what appear to be new infections and pneumonia. During most visits he ultimately spends a few days in the hospital to resolve his acute issues. On his most recent return to the long-term care facility, the medical staff approached the family about Mr. Hope’s code status. The family continues to insist on a full code status and that he be provided every opportunity to “live.” The staff is very concerned about Mr. Hope and his welfare. Many of the nursing staff have grown attached to him over the years, and watching him deteriorate has been distressing. They see part of their role as being his advocate and supporting him in ways that his own family has not. They express very strong reservations about performing CPR on Mr. Hope because they think it will be ineffective and they will have to break his upper extremities in order to gain access to his chest for resuscitation. The staff has contacted the ethics consultation service with the request that Mr. Hope needs protection and that his own family is not making the best decisions for him.
Colonial New Jersey's provincial fiscal structure, 1704–1775: spending obligations, revenue sources, and tax burdens during peace and war
Authors: Grubb Farley
Published: June 2016

I reconstitute the spending obligations and revenue sources of colonial New Jersey's provincial government for the years 1704 through 1775 from primary sources using forensic accounting techniques. I identify and analyze the methods for raising revenue to meet normal peacetime and emergency wartime expenses. I calculate the provincial tax burdens imposed on New Jersey's citizens. I identify how Britain interfered with New Jersey's fiscal structure. I estimate what the revenues and tax burdens would have been without this interference. New Jersey paid for war expenses by issuing bills of credit, spreading the tax burden of redeeming these bills into the future. New Jersey paid its yearly administrative costs with current property taxes and with current interest earnings from loaning paper money. In the absence of British interference and wars, New Jersey could have driven tax burdens to zero by using interest earnings to pay for all its provincial administrative costs.
A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being
Authors: Feast Alexandra , Moniz-Cook Esme , Stoner Charlotte , Charlesworth Georgina , Orrell Martin
Published: June 2016

Background:

Behavioral and psychological symptoms in dementia (BPSD) are important predictors of institutionalization as well as caregiver burden and depression. Previous reviews have tended to group BPSD as one category with little focus on the role of the individual symptoms. This review investigates the role of the individual symptoms of BPSD in relation to the impact on different measures of family caregiver well-being.

Methods:

Systematic review and meta-analysis of papers published in English between 1980 and December 2015 reporting which BPSD affect caregiver well-being. Paper quality was appraised using the Downs and Black Checklist (1998).

Results:

Forty medium and high quality quantitative papers met the inclusion criteria, 16 were suitable to be included in a meta-analysis of mean distress scores. Depressive behaviors were the most distressing for caregivers followed by agitation/aggression and apathy. Euphoria was the least distressing. Correlation coefficients between mean total behavior scores and mean distress scores were pooled for four studies. Irritability, aberrant motor behavior and delusions were the most strongly correlated to distress, disinhibition was the least correlated.

Conclusions:

The evidence is not conclusive as to whether some BPSD impact caregiver well-being more than others. Studies which validly examined BPSD individually were limited, and the included studies used numerous measures of BPSD and numerous measures of caregiver well-being. Future research may benefit from a consistent measure of BPSD, examining BPSD individually, and by examining the causal mechanisms by which BPSD impact well-being by including caregiver variables so that interventions can be designed to target BPSD more effectively.
A GENERALIZED STEADY-STATE GROWTH THEOREM
Authors: Irmen Andreas
Published: June 2016

Is there an economic justification for why technical change is by assumption labor-augmenting in dynamic macroeconomics? The literature on the endogenous choice of capital- and labor-augmenting technical change finds that technical change is purely labor-augmenting in steady state. The present paper shows that this finding is mainly an artifact of the underlying mathematical models. To make this point, Uzawa's steady-state growth theorem is generalized to a neoclassical economy that, besides consumption and capital accumulation, uses current output to create technical progress or to manufacture intermediates. The generalized steady-state growth theorem is shown to encompass four models of endogenous capital- and labor-augmenting technical change and the typical model of the induced innovations literature of the 1960s.
Is the pro-competition policy an effective solution for China’s public hospital reform?
Authors: Pan Jay , Qin Xuezheng , Hsieh Chee-Ruey
Published: June 2016

The new round of health care reforms in China achieved significant initial results. New and emerging problems coinciding with the deepening of the reforms, however, require further institutional changes to strengthen the competition mechanism and promote public hospital efficiency. This paper provides a conceptual framework and preliminary assessment of public hospital competition in China. Specifically, we distinguish between two closely related concepts – competition and privatization, and identify several critical conditions under which hospital competition can be used as a policy instrument to improve health care delivery in China. We also investigate the current performance and identify several unintended consequences of public hospital competition – mainly, medical arms race, drug over-prescription and the erosion of a trusting relationship between patients and physicians. Finally, we discuss the policy options for enhancing the internal competition in China’s hospital market, and conclude that public investment on information provision is key to reaping the positive outcomes of pro-competition policies.
Bat–man disease transmission: zoonotic pathogens from wildlife reservoirs to human populations
Authors: Allocati N , Petrucci A G , Di Giovanni P , Masulli M , Di Ilio C , De Laurenzi V
Published: June 2016

Bats are natural reservoir hosts and sources of infection of several microorganisms, many of which cause severe human diseases. Because of contact between bats and other animals, including humans, the possibility exists for additional interspecies transmissions and resulting disease outbreaks. The purpose of this article is to supply an overview on the main pathogens isolated from bats that have the potential to cause disease in humans.
Information recovery from low coverage whole-genome bisulfite sequencing
Authors: Libertini Emanuele , Heath Simon C. , Hamoudi Rifat A. , Gut Marta , Ziller Michael J. , Czyz Agata , Ruotti Victor , Stunnenberg Hendrik G. , Frontini Mattia , Ouwehand Willem H. , Meissner Alexander , Gut Ivo G. , Beck Stephan
Published: June 2016

The cost of whole-genome bisulfite sequencing (WGBS) remains a bottleneck for many studies and it is therefore imperative to extract as much information as possible from a given dataset. This is particularly important because even at the recommend 30X coverage for reference methylomes, up to 50% of high-resolution features such as differentially methylated positions (DMPs) cannot be called with current methods as determined by saturation analysis. To address this limitation, we have developed a tool that dynamically segments WGBS methylomes into blocks of comethylation (COMETs) from which lost information can be recovered in the form of differentially methylated COMETs (DMCs). Using this tool, we demonstrate recovery of ∼30% of the lost DMP information content as DMCs even at very low (5X) coverage. This constitutes twice the amount that can be recovered using an existing method based on differentially methylated regions (DMRs). In addition, we explored the relationship between COMETs and haplotypes in lymphoblastoid cell lines of African and European origin. Using best fit analysis, we show COMETs to be correlated in a population-specific manner, suggesting that this type of dynamic segmentation may be useful for integrated (epi)genome-wide association studies in the future.
A global reanalysis of storm surges and extreme sea levels
Authors: Muis Sanne , Verlaan Martin , Winsemius Hessel C. , Aerts Jeroen C. J. H. , Ward Philip J.
Published: June 2016

Extreme sea levels, caused by storm surges and high tides, can have devastating societal impacts. To effectively protect our coasts, global information on coastal flooding is needed. Here we present the first global reanalysis of storm surges and extreme sea levels (GTSR data set) based on hydrodynamic modelling. GTSR covers the entire world's coastline and consists of time series of tides and surges, and estimates of extreme sea levels. Validation shows that there is good agreement between modelled and observed sea levels, and that the performance of GTSR is similar to that of many regional hydrodynamic models. Due to the limited resolution of the meteorological forcing, extremes are slightly underestimated. This particularly affects tropical cyclones, which requires further research. We foresee applications in assessing flood risk and impacts of climate change. As a first application of GTSR, we estimate that 1.3% of the global population is exposed to a 1 in 100-year flood.
Radiocarbon evidence for enhanced respired carbon storage in the Atlantic at the Last Glacial Maximum
Authors: Freeman E. , Skinner L. C. , Waelbroeck C. , Hodell D.
Published: June 2016

The influence of ocean circulation changes on atmospheric CO2 hinges primarily on the ability to alter the ocean interior’s respired nutrient inventory. Here we investigate the Atlantic overturning circulation at the Last Glacial Maximum and its impact on respired carbon storage using radiocarbon and stable carbon isotope data from the Brazil and Iberian Margins. The data demonstrate the existence of a shallow well-ventilated northern-sourced cell overlying a poorly ventilated, predominantly southern-sourced cell at the Last Glacial Maximum. We also find that organic carbon remineralization rates in the deep Atlantic remained broadly similar to modern, but that ventilation ages in the southern-sourced overturning cell were significantly increased. Respired carbon storage in the deep Atlantic was therefore enhanced during the last glacial period, primarily due to an increase in the residence time of carbon in the deep ocean, rather than an increase in biological carbon export.
Direct measurement of proximity-induced magnetism at the interface between a topological insulator and a ferromagnet
Authors: Lee Changmin , Katmis Ferhat , Jarillo-Herrero Pablo , Moodera Jagadeesh S. , Gedik Nuh
Published: June 2016

When a topological insulator (TI) is in contact with a ferromagnet, both time-reversal and inversion symmetries are broken at the interface. An energy gap is formed at the TI surface, and its electrons gain a net magnetic moment through short-range exchange interactions. Magnetic TIs can host various exotic quantum phenomena, such as massive Dirac fermions, Majorana fermions, the quantum anomalous Hall effect and chiral edge currents along the domain boundaries. However, selective measurement of induced magnetism at the buried interface has remained a challenge. Using magnetic second-harmonic generation, we directly probe both the in-plane and out-of-plane magnetizations induced at the interface between the ferromagnetic insulator (FMI) EuS and the three-dimensional TI Bi2Se3. Our findings not only allow characterizing magnetism at the TI–FMI interface but also lay the groundwork for imaging magnetic domains and domain boundaries at the magnetic TI surfaces.
Pharmacological chaperone reshapes the energy landscape for folding and aggregation of the prion protein
Authors: Gupta Amar Nath , Neupane Krishna , Rezajooei Negar , Cortez Leonardo M. , Sim Valerie L. , Woodside Michael T.
Published: June 2016

The development of small-molecule pharmacological chaperones as therapeutics for protein misfolding diseases has proven challenging, partly because their mechanism of action remains unclear. Here we study Fe-TMPyP, a tetrapyrrole that binds to the prion protein PrP and inhibits misfolding, examining its effects on PrP folding at the single-molecule level with force spectroscopy. Single PrP molecules are unfolded with and without Fe-TMPyP present using optical tweezers. Ligand binding to the native structure increases the unfolding force significantly and alters the transition state for unfolding, making it more brittle and raising the barrier height. Fe-TMPyP also binds the unfolded state, delaying native refolding. Furthermore, Fe-TMPyP binding blocks the formation of a stable misfolded dimer by interfering with intermolecular interactions, acting in a similar manner to some molecular chaperones. The ligand thus promotes native folding by stabilizing the native state while also suppressing interactions driving aggregation.
Structure–function analysis of the extracellular domain of the pneumococcal cell division site positioning protein MapZ
Authors: Manuse Sylvie , Jean Nicolas L. , Guinot Mégane , Lavergne Jean-Pierre , Laguri Cédric , Bougault Catherine M. , VanNieuwenhze Michael S. , Grangeasse Christophe , Simorre Jean-Pierre
Published: June 2016

Accurate placement of the bacterial division site is a prerequisite for the generation of two viable and identical daughter cells. InStreptococcus pneumoniae, the positive regulatory mechanism involving the membrane protein MapZ positions precisely the conserved cell division protein FtsZ at the cell centre. Here we characterize the structure of the extracellular domain of MapZ and show that it displays a bi-modular structure composed of two subdomains separated by a flexible serine-rich linker. We further demonstratein vivothat the N-terminal subdomain serves as a pedestal for the C-terminal subdomain, which determines the ability of MapZ to mark the division site. The C-terminal subdomain displays a patch of conserved amino acids and we show that this patch defines a structural motif crucial for MapZ function. Altogether, this structure–function analysis of MapZ provides the first molecular characterization of a positive regulatory process of bacterial cell division.
Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia
Authors: Morimoto M , Lee E-Y , Zhang X , Inaba Y , Inoue H , Ogawa M , Shirasawa T , Yokosuka O , Miki T
Published: June 2016

Background/Objective:

Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial.

Methods:

We examined the antidiabetic effect of EPA in insulin receptor mutant (InsrP1195L/+) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia.

Results:

EPA supplementation was found to alleviate hyperglycemia of InsrP1195L/+ mice fed HFD (InsrP1195L/+/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in InsrP1195L/+ mice but not in wild-type mice, suggesting that InsrP1195L/+ mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of InsrP1195L/+ mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia.

Conclusions:

EPA exerts an antidiabetic effect in InsrP1195L/+/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia.
An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis
Authors: Sivaprakasam S , Gurav A , Paschall A V , Coe G L , Chaudhary K , Cai Y , Kolhe R , Martin P , Browning D , Huang L , Shi H , Sifuentes H , Vijay-Kumar M , Thompson S A , Munn D H , Mellor A , McGaha T L , Shiao P , Cutler C W , Liu K , Ganapathy V , Li H , Singh N
Published: June 2016

Composition of the gut microbiota has profound effects on intestinal carcinogenesis. Diet and host genetics play critical roles in shaping the composition of gut microbiota. Whether diet and host genes interact with each other to bring specific changes in gut microbiota that affect intestinal carcinogenesis is unknown. Ability of dietary fibre to specifically increase beneficial gut microbiota at the expense of pathogenic bacteria in vivo via unknown mechanism is an important process that suppresses intestinal inflammation and carcinogenesis. Free fatty acid receptor 2 (FFAR2 or GPR43) is a receptor for short-chain fatty acids (acetate, propionate and butyrate), metabolites of dietary fibre fermentation by gut microbiota. Here, we show FFAR2 is down modulated in human colon cancers than matched adjacent healthy tissue. Consistent with this, Ffar2−/− mice are hypersusceptible to development of intestinal carcinogenesis. Dietary fibre suppressed colon carcinogenesis in an Ffar2-dependent manner. Ffar2 played an essential role in dietary fibre-mediated promotion of beneficial gut microbiota, Bifidobacterium species (spp) and suppression of Helicobacter hepaticus and Prevotellaceae. Moreover, numbers of Bifidobacterium is reduced, whereas those of Prevotellaceae are increased in human colon cancers than matched adjacent normal tissue. Administration of Bifidobacterium mitigated intestinal inflammation and carcinogenesis in Ffar2−/− mice. Taken together, these findings suggest that interplay between dietary fibre and Ffar2 play a key role in promoting healthy composition of gut microbiota that stimulates intestinal health.
Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQQ209L-driven melanoma
Authors: Patel B R , Tall G G
Published: June 2016

The heterotrimeric G protein α subunit oncogenes GNAQ or GNA11 carry Q209X or R183X activating mutations and are present with ~90% frequency in human uveal melanomas. Forced expression of GNAQ/11Q209L in melanocytes is sufficient to drive metastatic melanoma in immune-compromised mice. No known drugs directly target these oncogenic G proteins. Ric-8A is the molecular chaperone that selectively folds Gαq/i/13 subunits. Targeting Ric-8A serves as a rational, yet unexplored approach to reduce the functional abundance of oncogenic Gαq/11 in order to blunt cancer signaling. Here, using mouse melanocyte cell graft tumorigenesis models, we determined that Ric-8A genetic ablation attenuated the abundance and melanoma-driving potential of Gαq-Q209L. A new conditional Ric-8AFlox/Flox; Rosa-CreER+/− mouse strain was derived and used as a tissue source to culture an immortalized, tamoxifen-inducible Ric-8A knockout melanocyte cell line that required 12-O-tetradecanoylphorbol-13-acetate (TPA, phorbol ester) for growth. The cell line failed to grow tumors when grafted into immune-compromised mice regardless of Ric-8A expression. Stable expression of human GNAQQ209L, but not GNAQWT in the cell line promoted TPA-independent cell proliferation, and upon cell grafting in mice, the initiation and robust growth of darkly-pigmented melanoma tumors. Deletion of Ric-8A in GNAQQ209L cells restored TPA-dependent growth, reduced Gαq-Q209L below detectable levels and completely mitigated tumorigenesis from primary or secondary cell line grafts. Interestingly, TPA treatment of cultured GNAQQ209L cells or host animals grafted with GNAQQ209L cells also sharply reduced Gαq-Q209L abundance and tumorigenic capacity. Finally, tumorigenesis initiated from GNAQQ209L cell grafts, followed by host mouse systemic tamoxifen treatment to delete Ric-8A in the grafted cells completely abrogated GNAQQ209L-driven tumor progression unless a stable human RIC-8A transgene was used to rescue the floxed Ric-8A alleles. Our work defines two new rational targets that may be developed as potential uveal melanoma therapies through reduction of Gαq/11-Q209L oncoprotein abundance: (1) Ric-8A inhibition and (2) phorbol ester treatment.
Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans
Authors: Czakai Kristin , Leonhardt Ines , Dix Andreas , Bonin Michael , Linde Joerg , Einsele Hermann , Kurzai Oliver , Loeffler Jürgen
Published: June 2016

Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungiAspergillus fumigatusandCandida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted withA. fumigatus, C. albicansor LPS was performed andKrüppel-like factor 4 (KLF4)was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.
Thioredoxin reductase 1 suppresses adipocyte differentiation and insulin responsiveness
Authors: Peng Xiaoxiao , Giménez-Cassina Alfredo , Petrus Paul , Conrad Marcus , Rydén Mikael , Arnér Elias S. J.
Published: June 2016

Recently thioredoxin reductase 1 (TrxR1), encoded by Txnrd1, was suggested to modulate glucose and lipid metabolism in mice. Here we discovered that TrxR1 suppresses insulin responsiveness, anabolic metabolism and adipocyte differentiation. Immortalized mouse embryonic fibroblasts (MEFs) lacking Txnrd1 (Txnrd1−/−) displayed increased metabolic flux, glycogen storage, lipogenesis and adipogenesis. This phenotype coincided with upregulated PPARγ expression, promotion of mitotic clonal expansion and downregulation of p27 and p53. Enhanced Akt activation also contributed to augmented adipogenesis and insulin sensitivity. Knockdown of TXNRD1 transcripts accelerated adipocyte differentiation also in human primary preadipocytes. Furthermore, TXNRD1 transcript levels in subcutaneous adipose tissue from 56 women were inversely associated with insulin sensitivity in vivo and lipogenesis in their isolated adipocytes. These results suggest that TrxR1 suppresses anabolic metabolism and adipogenesis by inhibition of intracellular signaling pathways downstream of insulin stimulation.
Correction: Corrigendum: Chemical nature of alkaline polyphosphate boundary film at heated rubbing surfaces
Authors: Wan Shanhong , Tieu A. Kiet , Zhu Qiang , Zhu Hongtao , Cui Shaogang , Mitchell David R. G. , Kong Charlie , Cowie Bruce , Denman John A. , Liu Rong
Published: June 2016

Scientific Reports 6: Article number: 26008; published online: 16 May 2016; updated: 27 June 2016. In this Article, Affiliation 6 is incorrectly listed as ‘Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, Australia’. The correct affiliation is listed below:
The Effects of Serum ANGPTL8/betatrophin on the Risk of Developing the Metabolic Syndrome – A Prospective Study
Authors: Wang Haoyu , Lai Yaxin , Han Cheng , Liu Aihua , Fan Chenling , Wang Hong , Zhang Hongmei , Ding Shuangning , Teng Weiping , Shan Zhongyan
Published: June 2016

ANGPTL8/betatrophin is a recently discovered hormone, which mainly synthesized and secreted by liver and adipose tissue, playing a critical role in pancreatic beta cell proliferation. Previous studies have suggested that serum ANGPTL8/betatrophin levels are associated with obesity and diabetes mellitus. Here, we evaluated the prospective association between ANGPTL8/betatrophin and the metabolic syndrome from a community-based cohort of 153 adults without metabolic syndrome. After 3.5-year follow-up, we observed an inverse correlation between the baseline ANGPTL8/betatrophin levels and the incidence of metabolic syndrome, even after multivariate adjustments. In receiver operating characteristic analysis, the area underneath the curve for ANGPTL8/betatrophin was 0.70 in males and 0.86 in females and the optimal cut-off values were 23.9 ng/mL and 31.1 ng/mL, respectively. This article suggests that ANGPTL8/betatrophin might be useful in predicting newly-onset metabolic syndrome and its progression in clinical setting.
Experimental Realization of a Reflections-Free Compact Delay Line Based on a Photonic Topological Insulator
Authors: Lai Kueifu , Ma Tsuhsuang , Bo Xiao , Anlage Steven , Shvets Gennady
Published: June 2016

Electromagnetic (EM) waves propagating through an inhomogeneous medium are generally scattered whenever the medium’s electromagnetic properties change on the scale of a single wavelength. This fundamental phenomenon constrains how optical structures are designed and interfaced with each other. Recent theoretical work indicates that electromagnetic structures collectively known as photonic topological insulators (PTIs) can be employed to overcome this fundamental limitation, thereby paving the way for ultra-compact photonic structures that no longer have to be wavelength-scale smooth. Here we present the first experimental demonstration of a photonic delay line based on topologically protected surface electromagnetic waves (TPSWs) between two PTIs which are the EM counterparts of the quantum spin-Hall topological insulators in condensed matter. Unlike conventional guided EM waves that do not benefit from topological protection, TPSWs are shown to experience multi-wavelength reflection-free time delays when detoured around sharply-curved paths, thus offering a unique paradigm for compact and efficient wave buffers and other devices.