bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape Pattern Analysis and Bayesian Modeling for Predicting Oncomelania hupensis Distribution in Eryuan County, People’s Republic of China
Authors: Yang Kun , Zhou Xiao-Nong , Wu Xiao-Hua , Steinmann Peter , Wang Xian-Hong , Yang Guo-Jing , Utzinger Jürg , Li Hong-Jun
Published: September 2018

Detailed knowledge of how local landscape patterns influence the distribution of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum, might facilitate more effective schistosomiasis control. We selected 12 villages in a mountainous area of Eryuan County, Yunnan Province, People’s Republic of China, and developed Bayesian geostatistical models to explore heterogeneities of landscape composition in relation to distribution of O. hupensis. The best-fitting spatio-temporal model indicated that the snail density was significantly correlated with environmental factors. Specifically, snail density was positively correlated with wetness and inversely correlated with the normalized difference vegetation index and mollusciciding, and snail density decreased as landscape patterns became more uniform. However, the distribution of infected snails was not significantly correlated with any of the investigated environmental factors and landscape metrics. Our enhanced understanding of O. hupensis ecology is important for spatial targeting of schistosomiasis control interventions.
Bone Hydatid Disease Refractory to Nitazoxanide Treatment
Authors: Schipper Hans G. , Simsek Suat , van Agtmael Michiel A. , van Lienden Krijn P.
Published: September 2018

We report a patient with bone hydatid disease that was refractory to both long-term daily treatment with albendazole, combined with cimetidine or administered as monotherapy (~15 years) and a relatively short course of nitazoxanide combined with albendazole (3 months). Despite continuous daily medical treatment, bone invasion and destruction proceeded. His pain and disability progressively increased.
Description of a Large Island-Wide Outbreak of Dengue in Puerto Rico, 2007
Authors: Tomashek Kay M. , Rivera Aidsa , Muñoz-Jordan Jorge L. , Hunsperger Elizabeth , Santiago Luis , Padro Oscar , Garcia Enid , Sun Wellington
Published: September 2018

Dengue is a mosquito-borne viral disease that affects 40% of the world’s population. Nearly four million U.S. citizens live in dengue-endemic areas; the most affected population resides in Puerto Rico. Data from a dengue surveillance system were used to describe all suspected cases reported in Puerto Rico in 2007. Rates of infection per 10,000 residents were calculated by age, sex, and residence. Rates and clinical outcomes were compared with those from outbreaks in 1994–1995 and 1998. In 2007, 10,508 suspected cases were reported; 52.5% persons were hospitalized, 31.8% reported hemorrhage, 2.2% had dengue hemorrhage fever, and 44 died. A total of 3,293 (33.0%) of processed specimens were laboratory positive for dengue virus (DENV); DENV-3 (1,342, 61.7%) and DENV-2 (677, 31.1%) were detected most often. The overall incidence of laboratory-positive dengue was 8.6 infections per 10,000 population. Rates were highest among persons 10–14 years of age (19.0), followed by persons 15–19 years of age (17.9) and infants (10.9). Higher rates of hospitalization and hemorrhage were reported in 2007 than in 1994–1995 or 1998. United States citizens residing in Puerto Rico are at risk of acquiring dengue. Data suggest that the severity is worsening, and persons 10–19 years of age and infants continue to be most affected.
Risk Factors Leading to Fatal Outcome in Scrub Typhus Patients
Authors: Lee Chang-Seop , Hwang Jeong-Hwan , Lee Heung-Bum , Kwon Keun-Sang
Published: September 2018

Scrub typhus is a potentially fatal infectious disease. However, to this date, no epidemiologic study on mortality of complicated scrub typhus has been reported. We reviewed the clinical records of 302 patients with diagnosis of scrub typhus who were admitted to our institute between January 2000 and December 2006. In total, 297 patients with scrub typhus were analyzed and the mortality rate of this study group was 6.1%. Multivariate logistic regression analysis revealed absence of eschar, event of intensive care unit admission and higher APACHE II score were independent predictive variables. Identification of these risk factors leading to fatal outcome may help physicians to start early intensive management of complicated scrub typhus.
Prevalence of Antimalarial Drug Resistance Mutations in Plasmodium vivax and P. falciparum from a Malaria-Endemic Area of Pakistan
Authors: Khatoon Lubna , Baliraine Frederick N. , Bonizzoni Mariangela , Malik Salman A. , Yan Guiyun
Published: September 2018

To study drug resistance in Bannu district, a malaria-endemic area in Pakistan, molecular-based analyses were undertaken. In Plasmodium vivax, antifolate resistance mutations were detected in pvdhfr gene codons 57, 58, and 117, with a 117N mutation frequency of 93.5%. All P. falciparum isolates exhibited double 59R + 108N mutations in pfdhfr, whereas the triple mutant 59R + 108N + 437G haplotype was found in 31.8% isolates. Furthermore, all (100%) P. falciparum isolates exhibited the key chloroquine resistance mutation, pfcrt 76T, which is also associated with resistance to amodiaquine. Additionally, pfmdr1 86Y and D1042Y mutations were, respectively, detected in 32% and 9% isolates. These results indicate an emerging multi-drug resistance problem in P. vivax and P. falciparum malaria parasites in Pakistan.
Infection of Mosquitoes with Plasmodium falciparum by Feeding on Humans and on Aotus Monkeys
Authors: Collins William E. , Jeffery Geoffrey M. , Sullivan JoAnn S. , Nace Douglas , Williams Tyrone , Galland G. Gale , Williams Allison , Barnwell John W.
Published: September 2018

Of 1,004 positive lots of mosquitoes fed on 229 humans infected with Plasmodium falciparum, 46.2% had 1–10 oocysts/(+)gut, 21.2% had 10–30 oocysts/(+)gut, 22.2% had 30–100 oocysts/(+)gut, and 10.4% had > 100 oocysts/(+) gut. The highest levels of infection occurred between 6 and 15 days after the peak in the asexual parasite count. Of 2,281 lots of Anopheles freeborni mosquitoes fed on splenectomized Aotus monkeys infected with the Santa Lucia strain of P. falciparum, 1,191 were infected (52.2%). The highest intensity infections ranged from 2.78 oocysts per positive gut in mosquitoes fed on Aotus vociferans to 6.08 oocysts per positive gut for those fed on A. lemurinus griseimembra to 10.4 oocysts per positive gut for those fed on A. nancymaae. The pattern of infection for mosquitoes fed on splenectomized Aotus monkeys was similar to that obtained by feeding on humans, but the intensity, based on oocyst/(+)gut, was much lower.
Tick-Borne Zoonotic Bacteria in Ticks Collected from Central Spain
Authors: Toledo Álvaro , Olmeda A. Sonia , Escudero Raquel , Jado Isabel , Valcárcel Félix , Casado-Nistal Miguel A. , Rodríguez-Vargas Manuela , Gil Horacio , Anda Pedro
Published: September 2018

The prevalence of tick-borne and related bacteria infecting adult ticks in central Spain was assessed by molecular methods. Six areas were sampled monthly during a 2-year longitudinal study. A total of 1,038 questing and 442 feeding ticks, belonging to eight different species, were tested. The most abundant species were Hyalomma lusitanicum (54% of captures), followed by Dermacentor marginatus (23%) and Rhipicephalus sanguineus (10%). Four human pathogens, including seven Rickettsia species, Anaplasma phagocytophilum, Borrelia burgdorferi, and Francisella tularensis, were detected at percentages of 19.0, 2.2, 1.7, and 0.5, respectively, whereas Bartonella spp. was never detected. In terms of infection and tick abundance, H. lusitanicum seems to be the most significant tick species in the area, carrying three of the five agents tested, and the anthropophilic tick, D. marginatum, infected with Rickettsia spp. and F. tularensis, is the most relevant in terms of public health. The significance of these data is discussed.
Cost-Effectiveness of a Community-Based Approach Intertwined with a Vertical Aedes Control Program
Authors: Baly Alberto , Toledo Maria Eugenia , Vanlerberghe Veerle , Ceballos Enrique , Reyes Alicia , Sanchez Idalmis , Carvajal Marinelli , Maso Rizel , La Rosa Maite , Denis Orestes , Boelaert Marleen , Van der Stuyft Patrick
Published: September 2018

We compared in a 5-year intervention study the cost-effectiveness of community-based environmental management intertwined with routine vertical Aedes control and of routine vertical control only. At baseline (year 2000), Aedes infestation levels and economic costs for vector control were comparable in intervention and control areas (house index, 2.23% versus 2.21% and US$21 versus US$24/yr/inhabitant, respectively). By 2004, house indices became 0.22% versus 2.36% and the costs were 29.8 US$ versus 36.7 US$/yr/inhabitant, respectively. The community cost made up 38.6% of the total economic cost in 2004 in the intervention areas against 23.5% in 2000. The average cost-effectiveness ratio for the intervention period 2001–2004, expressed as the societal cost incurred for the reduction (from baseline) of Aedes foci, was US$831.1 per focus in the intervention areas versus US$2,465.6 in the control areas. The intervention produced economic savings and health benefits that were sustained over the whole observation period.
Without heat and work - futher remarks on the Gyftopoulos-Beretta exposition of thermodynamics
Authors: BADUR Janusz , Feidt Michel , Ziółkowski Paweł
Published: September 2018

Developed during  recent two decades the new exposition of
thermodynamics developed by Gyfropoulos and Beretta [1] is aimed both to remove
logical circularities in teaching as well in removing obstacles for natural
generalization of this science.  Keeping
the line of reasoning, following Gyftopoulos and Beretta, we will introduce the
basic concepts of thermodynamics without the notion of “heat” and “work”, and
will extend the Gyftopoulos and Beretta exposition into three-dimensional
continuum thermodynamics [2]. In proposed approach notion of “energy” and
“energy interactions” play a dominant role. The main problem connected with the
internal energy concept as a form of ,,energy storage’’ and the transformations
of different forms of energy are discussed. Balance of energy is finally
presented as a sum of internal, kinetic, potential and electromagnetic energies
in the system that are compensated by the total energy flux, which consists of
work, heat, chemical, electrical, magnetical and radiative energy fluxes at the
system boundaries [3]. The law of energy (and mass) conservation can be
considered as the most important one which is superior over any other laws of
nature. An example of  “neo-classical”
Navier-Stokes equation, being a model thermodynamically consistent, is developed
and presented in details.
Crystal Violet Partitioning in Anionic Surfactants Micellar Media: UV-Visible Spectroscopy Study
Authors: OLASENİ S. E. , AKEREMALE O. A. , OSUNDİYA M. O. , ABOLUWOYE C. O. , ORUNESAJO A. , OYENEYİN O. E. , ONİYA E. O.
Published: September 2018

Simple and
differential Uv/Visible spectroscopic method were used to monitored the
interaction of Sodium dodecyl sulphate (SDS) and Sodium – N- laouryl sarcosinate (SLS) with crystal violet (CV) in pre-micellar
and post-micellar concentration range. The results showed that the peak of CV
at 590nm was unperturbed in CV/SDS system, but the intensity increased as surfactant
concentration increased, unlike in the CV/SLS system. This is an indication
that strong interaction occurred between CV and surfactants molecule.
Absorption data were also used to obtain partition coefficient () values and binding constant () values from which the free energy
of partition () and the free energy of binding () were estimated. From the partition coefficient () values, it could be inferred that the solubilization
of CV is more pronounced and spontaneous in the SDS than in the SLS micellar
media.
Effective temperature and performance characteristics of heat engines
Authors: HULEİHİL Mahmoud
Published: September 2018

For a heat engine working between
two heat reservoirs, a hot reservoir at high temperature TH
and a cold reservoir at low temperature TL, an effective
temperature and an effective efficiency are introduced.

The effective temperature is defined
as the square root of the ratio between the net work output of the heat engine wnet
and the SOT function (a new function introduced in this article).
The SOT function is defined as the negative of the cyclic
integral of the heat transfer change divided by the square of the temperature.

The effective efficiency of the heat
engine is defined (a novel definition) as one minus the ratio between the low
temperature and the effective temperature.

The effective temperature and the
effective efficiency are worked out in details for the Carnot heat engine and
the air standard cycles (Otto, Brayton, Stirling, and Ericsson).

It was found for the considered
cycles that the effective temperature is given by the expression () 

and the effective
efficiency is given by the expression () 

for all the considered
cycles.

The importance of these two proposed
measures is twofold: educational and they could be used as a quick tool by the
designer.
Strategies for Managing the Costs of Chronic Illness in the Context of Limited Financial Resources: A Qualitative Study in Dominican Persons With Arthritis
Authors: Nascimben Julia , Cubbison Caroline , Lape Emma C. , Katz Jeffrey N.
Published: September 2018

Objective

Persons who reside in low‐ and middle‐income countries often have insufficient resources to pay for treatments prescribed for their medical conditions. The aim of this study was to determine, using qualitative methods, how patients with arthritis in the Dominican Republic manage the costs associated with chronic illnesses.

Methods

We conducted individual interviews with 17 Dominican adults with advanced arthritis who were undergoing total knee replacement or total hip replacement at a hospital in Santo Domingo, Dominican Republic. Interviewers followed a moderator's guide with questions pertaining to the financial demands of arthritis treatment and the strategies participants used to pay for treatments. Interviews were audio recorded, transcribed verbatim, and translated into English. We used thematic analysis to identify salient themes.

Results

The thematic analysis suggested that health system factors (such as the extent of reimbursement for medications available in the public health care system) along with personal factors (such as disposable income) shaped individuals’ experiences of managing chronic illness. These systemic and personal factors contributed to a sizeable gap between the cost of care and the amount most participants were able to pay. Participants managed this resource gap using a spectrum of strategies ranging from acceptance (or, “making do with less”) to resourcefulness (or, “finding more”). Participants were aided by strong community bonds and religiously oriented resilience.

Conclusion

This qualitative study illuminates the range of strategies Dominican individuals with limited resources use to obtain health care and manage chronic illness. The findings raise hypotheses that warrant further study and could help guide provider–patient conversations regarding treatment adherence.
Backward Phase Matching for Second Harmonic Generation in Negative‐Index Conformal Surface Plasmonic Metamaterials
Authors: Liu Liangliang , Wu Lin , Zhang Jingjing , Li Zhuo , Zhang Baile , Luo Yu
Published: September 2018

Backward phase matching, which describes counterpropagating fundamental and harmonic waves in a negative‐index medium, is one of the most intriguing phenomena in nonlinear metamaterials. Predicted theoretically decades ago, however, it is still a challenging task to be applied for efficient second harmonic (SH) generation in a nonlinear metamaterial with ultrathin geometry and ultralow loss. Here, a negative‐index spoof plasmonic metamaterial is reported, which is composed of an ultrathin symmetrical corrugated metallic strips loaded with nonlinear active devices. The simulated and measured power spectra and surface near‐field distributions show that a peak SH signal can be generated at the backward phase‐matched frequency point in a 120° curved surface with high efficiency, thanks to the ultrathin flexible geometry, significant confinement effect, and large propagation length of the spoof surface plasmons. The results open new technological challenges from nano‐ and micro‐nonlinear photonics to science and engineering of compact, broadband, and efficient frequency‐mixing metamaterials and electromagnetic devices.
A Suicide Switch Directly Eliminates Intracellular scFv Oligomers in the Cytoplasm of Mammalian Cells
Authors: Nguyen Thuy Duong , Nagamune Teruyuki , Kawahara Masahiro
Published: September 2018

As intracellular antibodies (intrabodies) are highly promising tools for drug discovery, an innovative antibody screening platform in mammalian cells was previously developed by a single‐chain Fv (scFv)‐c‐kit growth sensor, which successfully selected rabies nucleoprotein and phosphoprotein‐specific intrabodies from a synthetic scFv library. Since the scFv‐c‐kit growth sensor releases a growth signal after forming oligomers due to binding to an oligomeric antigen, it is critical to use a library which does not contain self‐oligomeric scFvs to avoid the off‐target signal of the growth sensor. Here, a novel method to eliminate self‐oligomeric scFvs directly in the cytoplasm of mammalian cells is presented. A suicide switch by fusing an scFv with a cell‐death signaling domain to eliminate scFv oligomers is developed. It is found that among four cell‐death signaling domains, a suicide switch by fusing scFv with Fas‐associated death domain (FADD) can selectively reduce oligomeric scFvs. Furthermore, the library after eliminating scFv oligomers results in higher efficiency in the intrabody selection platform with a growth sensor. Collectively, the scFv‐FADD suicide switch can be applied to eliminate oligomeric scFvs from a library, which can consequently improve the quality of intracellular scFv libraries and accelerate the discovery of intrabodies in the future.
Polyethylenimine: A new differentiation factor to endothelial/cardiac tissue
Authors: Hosseinzadeh Simzar , Nazari Hojjatollah , Sadegzadeh Negar , Babaie Ali , Kabiri Mahboubeh , Tasharrofi Noshin , Soufi Zomorrod Mahsa , Soleimani Masoud
Published: September 2018

Among different tissues, endothelial/cardiac types require specific factors to promote myocardial regeneration after occurred injuries. Herein, cardiac stem cells (CSCs) as the major cell population that involved in cardiovascular repair were selected to study the role of polyethyleneimine (PEI) agent on endothelial differentiation. After preparation of electrospun network of PEI with polyacrylonitrile, the related characterizations were carried out including scanning electron microscope (SEM), field‐emission SEM, water contact angle, Fourier transform infrared spectroscopy and mechanical properties. Also, the release kinetic of the corresponding agent was studied up to 7 days. The cell differentiation studies were done in the following with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay, Real‐time polymerase chain reaction and immunostaining method. The whole obtained results approved the higher differentiation of CSCs into endothelial/cardiac cells. Finally, it is recommended that the PEI delivering increases the healing potency of CSCs and accordingly the regeneration speed of damaged cardiovascular tissue would be improved.
Association between PTCH1 and RAD54B single‐nucleotide polymorphisms and non‐syndromic orofacial clefts in a northern Chinese population
Authors: Liu Xiaotong , Yang Shaoyou , Meng Lingwei , Chen Chunyu , Hui Xiang , Jiang Yuxin , Jiao Xiaohui , Lv Kewen , Song Tao
Published: September 2018

Background

Non‐syndromic orofacial clefts (NSOC) is one of the most common congenital malformations, and its etiology involves both genetic and environmental factors. The present aimed to investigate the association of six single nucleotide polymorphisms (SNPs) (rs10512248 in PTCH1, rs12681366 and rs958447 in RAD54B, rs13317 in FGFR1, rs1838105 and rs4968247 in WNT9B) with NSOC in a Northern Chinese population.

Methods

In the present study, HI‐SNP technology was used to conduct genotyping of the six SNPs (rs10512248, rs12681366, rs957448, rs13317, rs1838105 and rs4968247) in 596 patients with NSOC and 466 healthy individuals from a Northern Chinese population.

Results

The results obtained indicated that rs10512248 and rs12681366 minor allele frequencies were statistically significant (p = 0.020 and 0.015, respectively). Statistical analysis confirmed that the CT genotype of RAD54B rs12681366 was associated with a decreased risk of NSOC (odds ratio = 0.62, 95% confidence interval = 0.46–0.82, P = 0.001). After correcting for multiple testing, the associations remained significant. By contrast, nonsignificant differences were found for the rs957448, rs13317, rs1838105 and rs4968247 allele and genotype frequencies between cases and controls.

Conclusions

These results demonstrate that the PTCH1 rs10512248 and RAD54B rs12681366 were significantly associated with NSOC in a Northern Chinese population. Additionally, the RAD54B rs12381366 CT genotype could decrease the risk of NSOC in a Northern Chinese population. We provide novel evidence for the development of NSOC in a Northern Chinese population.
First‐Trimester Diagnosis of Agnathia‐Otocephaly Complex: A Series of 4 Cases and Review of the Literature
Authors: Rodriguez Nadiezhda , Casasbuenas Alexandra , Andreeva Elena , Odegova Natalia , Wong Amy E. , Sepulveda Waldo
Published: September 2018

First‐trimester ultrasound findings in 4 fetuses with agnathia‐otocephaly complex are described. In addition, information from 3 cases reported in the literature was also reviewed, for a total of 7 cases analyzed. All 7 fetuses presented with agnathia and 6 with ventrocaudal displacement of the ears (melotia/synotia). Four fetuses had holoprosencephaly. In 6 cases, the parents opted for termination of pregnancy. The remaining case resulted in premature delivery at 26 weeks due to severe polyhydramnios and early neonatal death. This report highlights the important role of ultrasound in the identification of agnathia‐otocephaly complex in the first trimester of pregnancy.
Polyphenolic natural products and natural product–inspired steroidal mimics as aromatase inhibitors
Authors: Nielsen Alexander J. , McNulty James
Published: September 2018

The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this “phytoestrogenic” biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product–based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal‐based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor–positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges remain. This review highlights the aromatase activity of natural stilbenes, chalcones, and flavanones and synthetically inspired versions thereof and draws attention to new and under‐investigated areas within each class worthy of pursuit.
Progress in the application of CRISPR: From gene to base editing
Authors: Wu Wenyi , Yang Yanhui , Lei Hetian
Published: September 2018

The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR‐associated endonucleases (Cas) has been utilized for genome editing with great accuracy and high efficiency in generating gene knockout, knockin, and point mutations in eukaryotic genomes. However, traditional CRISPR/Cas9 technology introduces double‐stranded DNA breaks (DSBs) at a target locus as the first step to make gene corrections, which easily results in undesired mutations. Thus, it is necessary to develop new methods for correcting the unwanted mutations. In this review, we summarize the recent developments and a new approach to genome and base editing by using CRISPR/Cas9. This methodology renders a conversion of one target base into another, for example, C to T (or G to A), and A to G (or T to C) without producing DSBs, requiring a donor DNA template, or generating excessive insertions and deletions. Furthermore, CRISPR/Cas9‐derived base editing also improves efficiency in repairing point mutations in the genome.
Vorticity‐pressure formulations for the Brinkman‐Darcy coupled problem
Authors: Anaya Verónica , Mora David , Reales Carlos , Ruiz‐Baier Ricardo
Published: September 2018

We introduce a new variational formulation for the Brinkman‐Darcy equations formulated in terms of the scaled Brinkman vorticity and the global pressure. The velocities in each subdomain are fully decoupled through the momentum equations, and can be later recovered from the principal unknowns. A new finite element method is also proposed, consisting in equal‐order Nédélec and piecewise continuous elements, for vorticity and pressure, respectively. The error analysis for the scheme is carried out in the natural norms, with bounds independent of the fluid viscosity. An adequate modification of the formulation and analysis permits us to specify the presentation to the case of axisymmetric configurations. We provide a set of numerical examples illustrating the robustness, accuracy, and efficiency of the proposed discretization.
Impact of prenatal diagnosis of complex congenital heart disease on neonatal and infant morbidity and mortality
Authors: Chakraborty Abhishek , Gorla Sudheer R. , Swaminathan Sethuraman
Published: September 2018

Objectives

The objective of this study was to analyze the benefits associated with prenatal diagnosis of complex congenital heart disease (CHD) on preoperative morbidity, 30‐day and 1‐year mortality in this population.

Method

This was a retrospective review of patients with complex CHD born at our tertiary care center over a 10‐year period. Date analysis using Student t test and chi‐square test.

Results

The overall rate of prenatal detection of complex CHD was 68.1%. A steady increase in the number of complex CHD diagnosed prenatally was noted during the study period. The prenatal diagnosis of complex CHD was associated with significant reduction in the incidence of the following preoperative parameters: antibiotic use, mechanical ventilation, inotropic support, hepatic and renal dysfunction, and acidosis. These beneficial effects were more significant in ductal‐dependent cardiac anomalies. However, there were no neonatal and infant survival benefits in association with prenatal diagnosis.

Conclusion

Prenatal diagnosis of complex CHD leads to improved preoperative morbidity, especially in patients with ductal‐dependent cardiac anomalies. No survival benefits were noted with prenatal diagnosis of complex CHD.
Ethical and counseling challenges in prenatal exome sequencing
Authors: Harris Sarah , Gilmore Kelly , Hardisty Emily , Lyerly Anne Drapkin , Vora Neeta L.
Published: September 2018

Objective

Ethical and counseling challenges are expected with the introduction of prenatal whole exome sequencing. In this study, we describe specific challenges identified through the UNC‐Chapel Hill Prenatal Exome Sequencing Study.

Methods

Participants were a subset of women participating in the fetal exome study, which has enrolled 73 mother‐father‐fetus trios in pregnancies diagnosed with structural anomalies and normal standard genetic testing results. In this descriptive study, cases were reviewed by members of the research team, including a bioethicist, to identify counseling challenges. Illustrative cases were chosen by group consensus.

Results

Four illustrative cases were identified for further analysis. Challenges included need for adequate counseling and informed consent, challenges in prenatal variant interpretation, performing prenatal diagnosis in subsequent pregnancies, inability to identify a genetic etiology, and identifying parental secondary findings.

Conclusion

Our study illustrates several challenges identified in an ongoing prenatal exome study. While genomic medicine is a powerful tool for prenatal diagnosis, it is important that clinicians understand the ethical implications and parental perceptions of this testing modality.
Barrier Properties and Transcriptome Expression in Human iPSC-Derived Models of the Blood–Brain Barrier
Authors: Delsing Louise , Dönnes Pierre , Sánchez José , Clausen Maryam , Voulgaris Dimitrios , Falk Anna , Herland Anna , Brolén Gabriella , Zetterberg Henrik , Hicks Ryan , Synnergren Jane
Published: September 2018

Cell-based models of the blood–brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC-derived model of the BBB that includes endothelial cells in coculture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our coculture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non-permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in coculture, including upregulation of tight junction proteins, such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF, and PI3K-Akt pathways upon coculture. Our data suggest that coculture of iPSC-derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in coculture can be used to further improve iPSC-derived BBB models through selective pathway manipulation.
Open-string T-duality and applications to non-geometric backgrounds
Authors: Cordonier-Tello Fabrizio , Lüst Dieter , Plauschinn Erik
Published: September 2018

Abstract

We revisit T-duality transformations for the open string via Buscher’s procedure and work-out technical details which have been missing so far in the literature. We take into account non-trivial topologies of the world-sheet, we consider T-duality along directions with Neumann as well as Dirichlet boundary conditions, and we include collective T-duality along multiple directions.

We illustrate this formalism with the example of the three-torus with H-flux and its T-dual backgrounds, and we discuss global properties of open-string boundary conditions on such spaces.
Inferences of Mantle Viscosity Based on Ice Age Data Sets: The Bias in Radial Viscosity Profiles Due to the Neglect of Laterally Heterogeneous Viscosity Structure
Authors: Lau H. C. P. , Austermann J. , Mitrovica J. X. , Crawford O. , Al‐Attar D. , Latychev K.
Published: September 2018

Inferences of mantle viscosity using glacial isostatic adjustment (GIA) data are hampered by data sensitivity to the space‐time geometry of ice cover. A subset of GIA data is relatively insensitive to this ice history: the Fennoscandian relaxation spectrum (FRS), postglacial decay times in Canada and Scandinavia, and the rate of change of the degree‐2 zonal harmonic of the geopotential (
). These geographically limited data have been inverted to constrain the radial (one‐dimensional [1D]) mantle viscosity profile. We explore potential biases in these 1D inversions introduced by neglecting a three‐dimensional (3D) viscosity structure. We perform 1D Bayesian inversions of synthetic GIA data generated from Earth models with realistic 3D variations in mantle viscosity and lithospheric thickness and compare results to the 1D viscosity profile associated with the 3D model used to generate the synthetics. Differences between these two 1D profiles reflect GIA data resolution and biasing introduced by neglecting, in the inversions, a 3D viscosity structure. We focus on the second issue, demonstrating that the largest bias occurs within the upper mantle (in particular, the transition zone). This remains consistent when varying inversion parameters (e.g., prior/starting models) and the 1D/3D viscosity fields adopted in generating the synthetics. Inversions of individual data sets show 3D biasing increases for data exhibiting shallower (thus more localized) sensitivity to viscosity. Of the data considered herein, inversions of the FRS are subject to the largest bias followed by decay time data. The bias is minimal for
, as its deeper sensitivity is accompanied by broader averaging of structure in radial and lateral directions.
Synthesis of graphene quantum dots from natural polymer starch for cell imaging
Authors: Chen Weifeng , Li Dejiang , Tian Li , Xiang Wei , Wang Tianyuan , Hu Weimin , Hu Yulin , Chen Shaona , Chen Jianfeng , Dai Zhongxu
Published: September 2018

We have developed a facile route to synthesize GQDs with high PL emission by using starch as a precursor for the first time, and they are successfully applied in cell imaging.
Synthesis and proton conductivity of two novel molybdate polymers
Authors: Xu Li , Wang Zhifang , Lu Ying , Yan Tingting , Tian Hongrui , Li Xiaohui , Wang Shuang , Sun Xiuwei , Zhang Zhong , Dang Tianyi , Liu Shuxia
Published: September 2018

Two molybdate polymers H4[Co(phen)3]2[NaO(H2O)(l-Mo8O26)]2·2H2O (1) and H2[TEDA][Mo4O13]·3H2O (2) were synthesized, proton conductivity of 1 was 3.06 × 10−3 S cm−1.
Agricultural Microcredit for Tenant Farmers: Evidence from a Field Experiment in Bangladesh
Authors: Hossain Marup , Malek Mohammad Abdul , Hossain Md. Amzad , Reza Md. Hasib , Ahmed Md. Shakil
Published: September 2018

We study the impact of an agricultural microcredit program on the livelihoods of small, marginal, and landless tenant farmers in Bangladesh based on a Randomized Control Trial (RCT). Twenty percent of eligible households acquire at least one loan from the program within two years of the start of the intervention. Results show that access to credit has positive but imprecisely estimated effects on adoption of modern varieties (MV) of rice as well as rice yield. The microcredit program increases crop farm income but has no significant effect on total income or expenditure. Although the program does not have a significant effect on most economic outcomes, it demonstrates an increase in farm activities among the targeted farmers. Our study suggests that facilitating access to credit without addressing other constraints may not be enough to increase investment and profits of tenant farmers.
Developing and validating the Personal Risk of Oncogenic Human Papillomavirus infection score in US Women
Authors: Thai Thuy N , Bui Thanh C , Ebell Mark H
Published: September 2018

Background

Determining risk scores for genital high-risk human papillomavirus (HRHPV) infection in women will support more efficient cervical cancer screening strategies.

Objective

We developed and validated point scores to predict the likelihood of any genital HRHPV infection in women.

Methods

We conducted the cross-sectional analysis in 2017 and used data from the 2005–14 US National Health and Nutrition Examination Survey (7337 women aged 25–59 years; 6300 women aged 30–59 years). Predictors were reproductive health practices, risk behaviors and demographic variables. The outcome was a positive result for any of the 21 genital HRHPV genotypes. The 2005–12 cohorts were used as training and testing sets to develop scores that best classified women into three risk groups: low risk (<20%), average risk (20–30%) and high risk (>30%). The 2013–14 cohort was used to validate the final scores.

Results

Two-point scores with six self-reported variables were created to predict any HRHPV risks for the two age groups: the Personal Risk of Oncogenic HPV (PRO-HPV25) for women aged 25–59 years old and PRO-HPV30 for women aged 30–59 years old. The scores were successfully prospectively validated, with good calibration with regards to the predicted and observed rates of HRHPV infection. The scores had fair discrimination (c-statistics: 0.67–0.68).

Conclusion

The PRO-HPV risk scores can identify groups at low, average and high risk of genital HRHPV infection. This information can be used to prioritize women for cervical cancer screening in low-resource settings or to personalize screening intervals.
Normative Uncertainty and Social Choice
Authors: Tarsney Christian
Published: September 2018

In ‘Normative Uncertainty as a Voting Problem’, William MacAskill argues that positive credence in ordinal-structured or intertheoretically incomparable normative theories does not prevent an agent from rationally accounting for her normative uncertainties in practical deliberation. Rather, such an agent can aggregate the theories in which she has positive credence by methods borrowed from voting theory—specifically, MacAskill suggests, by a kind of weighted Borda count. The appeal to voting methods opens up a promising new avenue for theories of rational choice under normative uncertainty. The Borda rule, however, is open to at least two serious objections. First, it seems implicitly to ‘cardinalize’ ordinal theories, and so does not fully face up to the problem of merely ordinal theories. Second, the Borda rule faces a problem of option individuation. MacAskill attempts to solve this problem by invoking a measure on the set of practical options. But it is unclear that there is any natural way of defining such a measure that will not make the output of the Borda rule implausibly sensitive to irrelevant empirical features of decision-situations. After developing these objections, I suggest an alternative: the McKelvey uncovered set, a Condorcet method that selects all and only the maximal options under a strong pairwise defeat relation. This decision rule has several advantages over Borda and mostly avoids the force of MacAskill’s objection to Condorcet methods in general.
We Have No Reason to Think There Are No Reasons for Affective Attitudes
Authors: Faraci David
Published: September 2018

Barry Maguire argues that there are no reasons for affective attitudes. ‘There is no reason for your incredulous reaction to’ this thesis, he claims. In this paper, I argue that we have no reason to accept his thesis. I first examine Maguire's purported differences between reasons for action and so-called reasons for affective attitudes. In each case, I argue that the differences are exaggerated and that to the extent they obtain, they are best explained by differences between actions and affective attitudes, not between kinds of normative support. In closing, I argue that even if Maguire were correct, the extent of the threat to one of his central targets—so-called ‘buck-passing’ views—would remain unclear.
Minimum star-forming halo mass in axion cosmology
Authors: Sullivan James M , Hirano Shingo , Bromm Volker
Published: September 2018

Elucidating the particle physics nature of dark matter (DM) is one of the great challenges in modern science. The current lack of any direct DM detections in the laboratory heightens the need for astrophysical constraints, extending the search to DM models beyond the popular weakly interacting massive particle scenario. We here apply the classical Rees–Ostriker–Silk cooling criterion for galaxy formation to models with ultralight axion DM, also known as fuzzy dark matter (FDM). The resulting constraints provide a heuristic framework for upcoming observations, and our approximate analysis motivates the need for future self-consistent simulations of FDM structure formation. We use observational constraints for the DM hosts of ultra-faint dwarf (UFD) galaxies in the Local Group, together with the redshift constraints for the onset of primordial star formation from the recent EDGES 21-cm cosmology measurement, to illustrate this approach. We find that the existing constraints are straightforward to reconcile with standard ΛCDM, but disfavour FDM axion masses below ${\sim } 10^{-21}\, {\rm eV}/c^2$. The future potential for harnessing astrophysical probes of DM particle physics is compelling.
Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation
Authors: Masseya Joseph , Liua Yida , Alvarengaa Omar , Saeza Teresa , Schmerera Matthew , Warmflasha Aryeh
Published: September 2018

WNT/ß-catenin signaling is crucial to all stages of life. It controls early morphogenetic events in embryos, maintains stem-cell niches in adults, and is disregulated in many types of cancer. Despite its ubiquity, little is known about the dynamics of signal transduction or whether it varies across contexts. Here we probe the dynamics of signaling by monitoring nuclear accumulation of ß-catenin, the primary transducer of canonical WNT signals, using quantitative live-cell imaging. We show that ß-catenin signaling responds adaptively to constant WNT signaling in pluripotent stem cells, and that these dynamics become sustained upon differentiation. Varying dynamics were also observed in the response to WNT in commonly used mammalian cell-lines. Signal attenuation in pluripotent cells is controlled by both intra- and extra-cellular negative regulation of WNT signaling. TGFß-superfamily ligands Activin and BMP, which coordinate with WNT signaling to pattern the gastrula, increase the ß-catenin response in a manner independent of their ability to induce new WNT-ligand production. Our results reveal how variables external to the pathway, including differentiation status and crosstalk with other pathways, dramatically alter WNT/ß-catenin dynamics.
Polyploid plants have faster rates of multivariate climatic niche evolution than their diploid relatives
Authors: Baniaga Anthony E. , Marx Hannah E. , Arrigo Nils , Barker Michael S.
Published: September 2018

Whole genome duplication is an important evolutionary process in plants. In contrast to other speciation mechanisms, polyploid species begin with substantial postzygotic reproductive isolation from progenitors while being sympatric with one or both. These nascent polyploid species often go extinct due to ecological and evolutionary genetic obstacles. Interestingly, polyploid species appear to quickly occupy different geographic distributions and ecological niches than their diploid progenitors. Using biogeographic data from polyploid and diploid species representing 49 genera of vascular plants, we tested whether climatic niches of polyploid species evolve faster than their diploid relatives. We found polyploid species often have less climatic overlap than expected with diploid progenitors. Consistent with this pattern, we estimated that the climatic niches of polyploid plants consistently evolved faster than the niches of diploid relatives. Our results indicate ecological niche differentiation is important for polyploid establishment, and suggest ecological differentiation is important for speciation processes more widely.

Statement of Authorship

AB and MS conceived of project, AB and NA generated the dataset, AB and HM performed analyses, AB and MS cowrote manuscript.

Data Accessibility Statement

Upon acceptance all necessary R scripts, data, and files supporting the results will be archived on FigShare with the data DOI included at the end of the article.
Patients’ accounts of memory lapses in interactions between neurologists and patients with functional memory disorders
Authors: Alexander Marc , Blackburn Daniel , Reuber Markus
Published: September 2018

One of the most commonly made diagnoses in secondary care memory services is functional memory disorder (FMD). FMD is non‐progressive and characterised by persistent worries about memory failures without objective evidence of cognitive impairment. This study explores how patients with FMD present their memory concerns. Utilizing video recordings of consultations between patients and neurologists in a memory clinic, we show that FMD patients account for their memory deficits as significant disruptions to their daily lives. Resonating with research which identified a dissonance between self‐reports of memory functioning by FMD patients and the outcome of neuropsychological assessments, we demonstrate that, in giving a detailed account of their perceived memory problems, patients provide objective conversational evidence of their cognitive and memory capacity, implicitly undermining the claim of an objective problem. Using conversation analysis, we examine three of the more prominent interactional practices FMD patients draw on when attempting to communicate memory deficits to the doctor – they are (i) contrasts with a standard of ‘normal’; (ii) third‐party observations; and (iii) direct reported speech. These interactional features are recurrent devices for displaying memory concerns as legitimate problems, embedded within patients’ accounts of their day‐to‐day lives.
House dust mite‐driven neutrophilic airway inflammation in mice with TNFAIP3‐deficient myeloid cells is IL‐17‐independent
Authors: Vroman Heleen , Das Tridib , Bergen Ingrid M. , van Hulst Jennifer A. C. , Ahmadi Fatemeh , van Loo Geert , Lubberts Erik , Hendriks Rudi W. , Kool Mirjam
Published: September 2018

Background

Asthma is a heterogeneous disease of the airways that involves several types of granulocytic inflammation. Recently, we have shown that the activation status of myeloid cells regulated by TNFAIP3/A20 is a crucial determinant of eosinophilic or neutrophilic airway inflammation. However, whether neutrophilic inflammation observed in this model is dependent on IL‐17 remains unknown.

Objective

In this study, we investigated whether IL‐17RA‐signalling is essential for eosinophilic or neutrophilic inflammation in house dust mite (HDM)‐driven airway inflammation.

Methods

Tnfaip3fl/flxLyz2+/cre (Tnfaip3LysM‐KO) mice were crossed to Il17raKO mice, generating Tnfaip3LysMIl17raKO mice and subjected to an HDM‐driven airway inflammation model.

Results

Both eosinophilic and neutrophilic inflammation observed in HDM‐exposed WT and Tnfaip3LysM‐KO mice respectively were unaltered in the absence of IL‐17RA. Production of IL‐5, IL‐13 and IFN‐γ by CD4+ T cells was similar between WT, Tnfaip3LysM‐KO and Il17raKO mice, whereas mucus‐producing cells in Tnfaip3LysM‐KOIl17raKO mice were reduced compared to controls. Strikingly, spontaneous accumulation of pulmonary Th1, Th17 and γδ‐17 T cells was observed in Tnfaip3LysM‐KOIl17raKO mice, but not in the other genotypes. Th17 cell‐associated cytokines such as GM‐CSF and IL‐22 were increased in the lungs of HDM‐exposed Tnfaip3LysM‐KOIl17raKO mice, compared to IL‐17RA‐sufficient controls. Moreover, neutrophilic chemo‐attractants CXCL1, CXCL2, CXCL12 and Th17‐promoting cytokines IL‐1β and IL‐6 were unaltered between Tnfaip3LysM‐KO and Tnfaip3LysM‐KOIl17raKO mice.

Conclusion and Clinical Relevance

These findings show that neutrophilic airway inflammation induced by activated TNFAIP3/A20‐deficient myeloid cells can develop in the absence of IL‐17RA‐signalling. Neutrophilic inflammation is likely maintained by similar quantities of pro‐inflammatory cytokines IL‐1β and IL‐6 that can, independently of IL‐17‐signalling, induce the expression of neutrophil chemo‐attractants.