bluuebunny/crossref_metadata_2025 huggingface dataset:
A realist review of one‐to‐one breastfeeding peer support experiments conducted in developed country settings
Authors: Trickey Heather , Thomson Gill , Grant Aimee , Sanders Julia , Mann Mala , Murphy Simon , Paranjothy Shantini
Published: December 2017

The World Health Organisation guidance recommends breastfeeding peer support (BFPS) as part of a strategy to improve breastfeeding rates. In the UK, BFPS is supported by National Institute for Health and Care Excellence guidance and a variety of models are in use. The experimental evidence for BFPS in developed countries is mixed and traditional methods of systematic review are ill‐equipped to explore heterogeneity, complexity, and context influences on effectiveness. This review aimed to enhance learning from the experimental evidence base for one‐to‐one BFPS intervention. Principles of realist review were applied to intervention case studies associated with published experimental studies. The review aimed (a) to explore heterogeneity in theoretical underpinnings and intervention design for one‐to‐one BFPS intervention; (b) inform design decisions by identifying transferable lessons developed from cross‐case comparison of context‐mechanism‐outcome relationships; and (c) inform evaluation design by identifying context‐mechanism‐outcome relationships associated with experimental conditions. Findings highlighted poor attention to intervention theory and considerable heterogeneity in BFPS intervention design. Transferable mid‐range theories to inform design emerged, which could be grouped into seven categories: (a) congruence with local infant feeding norms, (b) integration with the existing system of health care, (c) overcoming practical and emotional barriers to access, (d) ensuring friendly, competent, and proactive peers, (e) facilitating authentic peer–mother interactions, (f) motivating peers to ensure positive within‐intervention amplification, and (g) ensuring positive legacy and maintenance of gains. There is a need to integrate realist principles into evaluation design to improve our understanding of what forms of BFPS work, for whom and under what circumstances.
Acceptability of multiple micronutrient powders and iron syrup in Bihar, India
Authors: Young Melissa F. , Girard Amy Webb , Mehta Rukshan , Srikantiah Sridhar , Gosdin Lucas , Menon Purnima , Ramakrishnan Usha , Martorell Reynaldo , Avula Rasmi
Published: December 2017

Nearly two thirds of young children are anaemic in Bihar, India. Paediatric iron and folic acid syrup (IFAS) and multiple micronutrient powders (MNPs) are two evidence‐based interventions to prevent anaemia. Using a randomized crossover design, we examined the acceptability of IFAS versus MNPs for children 6–23 months. In a catchment area of 2 health centres in Bihar, health front‐line workers (FLWs) delivered either (a) IFAS twice weekly or (b) MNPs for 1 month followed by the other supplementation strategy for 1 month to the same families (NCT02610881). Household surveys were conducted at baseline (N = 100), 1 month after receiving the first intervention (1 month; N = 95), and 1 month after the second intervention (2 months; N = 93). Focus group discussions (10 FLWs) and in‐depth interviews (20 mothers) were held at 1 and 2 months. We used chi‐square and Fisher exact tests to test mothers' product preferences. Qualitative data were analysed using MaxQDA and Excel employing a thematic analysis approach. There was high adherence and acceptability for both products (>80%). There was no significant difference in preference (p < .05) on perceived benefits (39% MNPs, 40% IFAS), side effects (30% MNPs, 30% IFAS), ease of use (42% IFAS, 31% MNPs), child preference (45% IFAS, 37% MNPs), and maternal preference (44% IFAS, 34% MNPs). Mothers and FLWs indicated that the direct administration of IFAS ensured that children consumed the full dose, and MNPs intake depended on the quantity of food consumed, especially among younger children, which emphasizes the need to integrate supplementation with the promotion of optimal child feeding practices.
Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion
Authors: Smit Bob , Smulders Yvo M. , Eringa Etto C. , Gelissen Harry P. M. M. , Girbes Armand R. J. , de Grooth Harm‐Jan S. , Schotman Hans H. M. , Scheffer Peter G. , Oudemans‐van Straaten Heleen M. , Spoelstra‐de Man Angelique M. E.
Published: December 2017

Objective

To determine the human dose‐response relationship between a stepwise increase in arterial oxygen tension and its associated changes in DO2 and sublingual microcirculatory perfusion.

Methods

Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume‐clamp method. At the end of each period, the sublingual microcirculation was assessed by SDF.

Results

Systemic DO2 was unchanged throughout the study (Pslope = .8). PVD decreased in a sigmoidal fashion (max −15% while breathing oxygen, SD18, Pslope = .001). CI decreased linearly (max −10%, SD10, Pslope < .001) due to a reduction in HR (max −10%, SD7, Pslope = .009). There were no changes in stroke volume or MAP. Most changes became apparent above an arterial oxygen tension of 20 kPa.

Conclusions

In healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic DO2. Sublingual microcirculatory PVD decreased in a dose‐dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa.
Sex‐related differences in the postmolt distribution of Weddell seals (Leptonychotes weddellii) in the southern Weddell Sea
Authors: Langley Izzy , Fedak Mike , Nicholls Keith , Boehme Lars
Published: December 2017

The population of Weddell seals (Leptonychotes weddellii) in the southern Weddell Sea is in a unique position on the continental shelf edge, with vast shelf waters to the south, and deep Southern Ocean to the north. We describe sex‐related differences in the winter distribution of this population, from data collected by 20 conductivity‐temperature‐depth satellite relay data loggers deployed in February 2011 at the end of the annual molt. The regional daily speed was calculated, and a state‐space model was used to estimate behavioral states to positions along individuals’ tracks. GLMMs estimated that males and smaller individuals, diving in shallower water, traveled less far per day of deployment (males 14.6 ± 2.26 km/d, females 18.9 ± 2.42 km/d), and males were estimated to dive in shallower water (males 604 ± 382 m, females 1,875 ± 1,458 m). Males and smaller individuals were also estimated to be more resident; males spent an average 83.4% ± 7.7% of their time in a resident behavioral state, compared to females at 74.1% ± 7.1%. This evidence that male and female Weddell seals in the southern Weddell Sea are adopting different strategies has not been shown elsewhere along their circumpolar distribution.
Brachionidium elzbietae and B. dorisiae spp. nov. (Orchidaceae) from Colombia
Authors: Kolanowska Marta , Rykaczewski Max , Medina Trejo Ramiro , Szlachetko Dariusz L.
Published: December 2017

Two new species of the orchid genus Brachionidium are described and illustrated based on Colombian material. Both novelties are relatively large, stout and erect plants characterized by the presence of a glabrous callus lip. Brachionidium elzbietae sp. nov. resembles B. tuberculatum from which it differs by the long‐tailed sepals and lip lacking a glenion. Brachionidium dorisiae sp. nov. is similar to B. fornicatum, but is easily distinguished by its larger and shortly bifid synsepal. A key to identification of Colombian representatives of Brachionidium is provided the morphology of new species and their relatives is compared.
Outcome in patients with left common pulmonary vein after cryoablation with second‐generation cryoballoon
Authors: Beiert Thomas , Lodde Pia C. , Linneborn Lutz P.T. , Werner Jessica , Prinz Lisa , Stöckigt Florian , Linhart Markus , Lickfett Lars , Nickenig Georg , Schrickel Jan W. , Andrié René P.
Published: December 2017

Background

Pulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF).

Hypothesis

AF‐free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second‐generation cryoballoon.

Methods

We included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3‐month blanking period.

Results

We observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow‐up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P  =  0.051) and Kaplan‐Meier analysis showed lower AF‐free survival in patients with existence of a LCPV (P  =  0.028). At 1‐year follow‐up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence.

Conclusion

Patients with LCPV had significantly reduced AF‐free survival after ablation with the second‐generation cryoballoon, despite similar acutely successful PVIs.
Longitudinal Relationships Between Positive Affect, Loneliness, and Suicide Ideation: Age‐Specific Factors in a General Population
Authors: Bennardi Marco , Caballero Francisco Félix , Miret Marta , Ayuso‐Mateos Jose Luis , Haro Josep Maria , Lara Elvira , Arensman Ella , Cabello Maria
Published: December 2017

The aims of this study were to analyze whether positive and negative affect, social support, and loneliness are factors longitudinally related to suicide ideation in the general population in different age groups. A total of 2,392 individuals from a nationally representative sample of the Spanish general population were evaluated in 2011–2012 and in 2014–2015. After including relevant control variables in the analyses, lower positive affect was prospectively related to ideation in 18‐ to 59‐year‐old individuals, whereas feelings of loneliness were related to ideation in 60‐year‐and‐older individuals. Social support was not associated with suicide ideation in any age group. These results are in line with the need for age‐tailored suicide prevention programs. The present findings might also suggest that health care professionals should consider feelings of loneliness rather than social support to assess the presence of suicide ideation in older people.
The poor “sociological imagination” of the rich: Explaining attitudinal divergence towards welfare, inequality, and redistribution
Authors: Edmiston Daniel
Published: December 2017

Quantitative research has tended to explain attitudinal divergence towards welfare and redistribution through self‐interested rationalities. However, such an approach risks abstracting individuals from the structural determinants of resource allocation and biographical experience. With that in mind, this article draws on a qualitative study of 50 individuals experiencing relative deprivation and affluence in the United Kingdom and New Zealand to examine how lived experiences of inequality affect attitude formation towards welfare and redistribution. Scenario‐driven vignettes were used to stimulate an applied discussion of abstract principles pertaining to welfare and inequality. Use of this methodological device proffered novel insight into the phenomenological effects of material position on public attitudes and policy preferences in a comparative context. The findings suggest that affluent individuals are less likely to acknowledge systemic features shaping socioeconomic life. As a result, they exhibit a poor sociological imagination that is deployed in distinct and patterned ways to make sense of, and at times justify, economic restructuring. By contrast, those living in relative deprivation are more likely to advance accounts of intergroup relations and social location that emphasize the structuration of (dis‐)advantage. Based on the findings, policy and political implications are considered for welfare and redistribution amidst rising structural inequality.
A heuristic‐based approach to mitigating positional errors in patrol data for species distribution modeling
Authors: Zhang Guiming , Zhu A‐Xing , Huang Zhi‐Pang , Xiao Wen
Published: December 2017

Species distribution modeling (SDM) at fine spatial resolutions requires species occurrence data of high positional accuracy to achieve good model performance. However, wildlife occurrences recorded by patrols in ranger‐based monitoring programs suffer from positional errors, because recorded locations represent the positions of the ranger and differ from the actual occurrence locations of wildlife (hereinafter referred to as positional errors in patrol data). This study presented an evaluation of the impact of such positional errors in patrol data on SDM and developed a heuristic‐based approach to mitigating the positional errors. The approach derives probable wildlife occurrence locations from ranger positions, utilizing heuristics based on species preferred habitat and the observer's field of view. The evaluations were conducted through a case study of SDM using patrol records of the black‐and‐white snub‐nosed monkey (Rhinopithecus bieti) in Yunnan, China. The performance of the approach was also compared against alternative sampling methods. The results showed that the positional errors inR. bietipatrol data had an adverse effect on SDM performance, and that the proposed approach can effectively mitigate the impact of the positional errors to greatly improve SDM performance.
A novel association between high red blood cell alloimmunization rates and hereditary hemorrhagic telangiectasia
Authors: Zheng Yan , Pollak Jeffrey , Henderson Katharine , Hendrickson Jeanne E. , Tormey Christopher A.
Published: December 2017

BACKGROUND

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder associated with multiple arteriovenous malformations. HHT patients may require red blood cell (RBC) transfusion due to spontaneous hemorrhage or surgical bleeding. Because HHT‐associated hemorrhage often occurs in submucosa we hypothesized that RBC alloimmunization rates in HHT patients may be higher than those observed in other transfused patients and investigated this in a retrospective study.

STUDY DESIGN AND METHODS

Eighty‐five patients with HHT who were transfused at our tertiary care facility were identified. A group of randomly selected, chronically transfused patients without HHT were used as controls (n = 207). RBC transfusion and alloantibody data were extracted from medical records.

RESULTS

Alloimmunization rates among patients with HHT were significantly higher than those of controls (15.29% vs. 2.42%; p < 0.001), while HHT patients received fewer RBC transfusions at our institution compared to controls (4.27 units vs. 8.84 units; p < 0.0001). Anti‐E, ‐K, and ‐c were the three most common alloantibodies identified in HHT patients. There was a trend for HHT patients to make more antibodies per alloimmunized patient than controls (2.38 alloantibodies vs. 1.60 alloantibodies), although this difference was not significant (p = 0.37).

CONCLUSION

To our knowledge, this is the first study to evaluate RBC alloimmunization rates in patients with HHT. It is unclear whether the high alloimmunization rates observed are due to lifetime transfusion burden, underlying disease pathophysiology, or other variables. Additional studies are needed to evaluate the generalizability of our findings to other HHT populations and to consider the utility of prophylactic antigen matching for C/E/K.
Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating
Authors: Fujii Naoto , Meade Robert D. , McNeely Brendan D. , Nishiyasu Takeshi , Sigal Ronald J. , Kenny Glen P.
Published: December 2017

New Findings

What is the central question of this study?

It remains to be determined whether type 2 diabetes attenuates muscarinic and nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation.

What is the main finding and its importance?

We show that type 2 diabetes specifically attenuates purinergic cutaneous vasodilatation without influencing muscarinic and nicotinic cutaneous vasodilatation and sweating. Our results provide valuable new information regarding the receptor‐specific influence of type 2 diabetes on microvascular and sudomotor function.

The present study evaluated whether type 2 diabetes (T2D) attenuates muscarinic and/or nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation. Cutaneous vascular conductance and sweat rate were evaluated in 12 healthy non‐diabetic older adults (Control, 60 ± 8 years) and 13 older adults with T2D (62 ± 10 years) at three intradermal forearm skin sites perfused with the following: (i) methacholine (muscarinic receptor agonist, five doses: 0.0125, 0.25, 5, 100 and 2000 mm); (ii) nicotine (nicotinic receptor agonist, five doses: 1.2, 3.6, 11, 33 and 100 mm); or (iii) ATP (purinergic receptor agonist, five doses: 0.03, 0.3, 3, 30 and 300 mm). Each agonist was administered for 25 min per dose. At the end of the protocol, 50 mm sodium nitroprusside was administered to all skin sites to elicit maximal cutaneous vasodilatation. Cutaneous vascular conductance during methacholine and nicotine administration did not differ between groups (all P > 0.05). In contrast, cutaneous vascular conductance during administration of 30 mm (42 ± 28 versus 63 ± 26% maximum, P ≤ 0.05) and 300 mm ATP (56 ± 24 versus 71 ± 20% maximum, P ≤ 0.05) was attenuated in individuals with T2D in comparison to the Control participants. Furthermore, cutaneous vascular conductance during administration of 50 mm sodium nitroprusside was lower in individuals with T2D relative to Control subjects (P = 0.04). Methacholine‐ and nicotine‐induced sweating was similar between groups (all P > 0.05). Thus, T2D attenuates purinergic cutaneous vasodilatation without affecting muscarinic and nicotinic cutaneous vascular and sweating responses.
Ca2+ and lipid signals hold hands at endoplasmic reticulum–plasma membrane contact sites
Authors: Balla Tamas
Published: December 2017

Discovery of the STIM1 and Orai proteins as the principal components of store‐operated Ca2+ entry has drawn attention to contact sites between the endoplasmic reticulum (ER) and the plasma membrane (PM). Such contacts between adjacent membranes of different cellular organelles, primarily between the mitochondria and the ER, had already been known as the sites where Ca2+ released from the ER can be efficiently channelled to the mitochondria and also where phosphatidylserine synthesis and transfer takes place. Recent studies have identified contact sites between virtually every organelle and the ER and the functional importance of these small specialized membrane domains is increasingly recognized. Most recent developments have highlighted the role of phosphatidylinositol 4‐phosphate gradients as critical determinants of the non‐vesicular transport of various lipids from the ER to other organelles such as the Golgi or PM. As we learn more about membrane contact sites it becomes apparent that Ca2+ is not only transported at these sites but also controls both the dynamics and the lipid transfer efficiency of these processes. Conversely, lipids are critical for regulating the Ca2+ entry process. This review will summarize some of the most exciting recent developments in this rapidly expanding research field.

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Bifurcations in valveless pumping techniques from a coupled fluid-structure-electrophysiology model in heart development
Authors: Battista Nicholas Anthony , Miller Laura Ann
Published: December 2017

We explore an embryonic heart model that couples electrophysiology and muscle-force generation to flow induced using a $2D$ fluid-structure interaction framework based on the immersed boundary method. The propagation of action potentials are coupled to muscular contraction and hence the overall pumping dynamics. In comparison to previous models, the electro-dynamical model does not use prescribed motion to initiate the pumping motion, but rather the pumping dynamics are fully coupled to an underlying electrophysiology model, governed by the FitzHugh-Nagumo equations. Perturbing the diffusion parameter in the FitzHugh-Nagumo model leads to a bifurcation in dynamics of action potential propagation. This bifurcation is able to capture a spectrum of different pumping regimes, with dynamic suction pumping and peristaltic-like pumping at the extremes. We find that more bulk flow is produced within the realm of peristaltic-like pumping.
Hybrid Processes in Additive Manufacturing
Authors: Sealy Michael P. , Madireddy Gurucharan , Williams Robert E. , Rao Prahalada , Toursangsaraki Maziar
Published: December 2017

Hybrid additive manufacturing (hybrid-AM) has described hybrid processes and machines as well as multimaterial, multistructural, and multifunctional printing. The capabilities afforded by hybrid-AM are rewriting the design rules for materials and adding a new dimension in the design for additive manufacturing (AM) paradigm. This work primarily focuses on defining hybrid-AM in relation to hybrid manufacturing (HM) and classifying hybrid-AM processes. Hybrid-AM machines, materials, structures, and function are also discussed. Hybrid-AM processes are defined as the use of AM with one or more secondary processes or energy sources that are fully coupled and synergistically affect part quality, functionality, and/or process performance. Historically, defining HM processes centered on process improvement rather than improvements to part quality or performance; however, the primary goal for the majority of hybrid-AM processes is to improve part quality and part performance rather than improve processing. Hybrid-AM processes are typically a cyclic process chain and are distinguished from postprocessing operations that do not meet the fully coupled criterion. Secondary processes and energy sources include subtractive and transformative manufacturing technologies, such as machining, remelting, peening, rolling, and friction stir processing (FSP). As interest in hybrid-AM grows, new economic and sustainability tools are needed as well as sensing technologies that better facilitate hybrid processing. Hybrid-AM has ushered in the next evolutionary step in AM and has the potential to profoundly change the way goods are manufactured.
Probabilistic Elastic Element Design for Robust Natural Dynamics of Structure-Controlled Variable Stiffness Actuators
Authors: Stuhlenmiller Florian , Schuy Jochen , Beckerle Philipp
Published: December 2017

This paper proposes a probabilistic approach for the design of elastic elements to be used in structure-controlled variable stiffness actuators (VSA) for robotic applications. Considering the natural dynamics of the elastic actuation system, requirements are defined and material selection as well as geometry calculation are performed using lumped parameter models. Monte Carlo simulations are integrated in the design procedure to ensure a robust implementation of the required dynamical characteristics. Thereby, effects of uncertainties that might be caused by manufacturing or deviations of material properties are taken into account. To validate the suitability of the overall approach and the particular methods, a torsional elastic element is implemented and experimentally evaluated. The evaluation shows a fulfillment of the key requirements, i.e., specific natural dynamic behavior, that is only achieved due to considering uncertainties. Further, the transferability of the approach to other structure-controlled elastic actuators is discussed and implications are given. Only the governing equations of stiffness properties in certain load situation need to be adapted, e.g., from torsion to bending. Due to the simple transfer, the proposed probabilistic and model-based approach is promising for application to various actuator concepts with structure-controlled variable stiffness.
Leader-Following Consensus Control of General Linear Multi-Agent Systems With Diverse Time-Varying Input Delays
Authors: Yuan Chengzhi
Published: December 2017

This paper addresses the problem of leader-following consensus control of general linear multi-agent systems (MASs) with diverse time-varying input delays under the integral quadratic constraint (IQC) framework. A novel exact-memory distributed output-feedback delay controller structure is proposed, which utilizes not only relative estimation state information from neighboring agents but also local real-time information of time delays and the associated dynamic IQC-induced states from the agent itself for feedback control. As a result, the distributed consensus problem can be decomposed into H∞ stabilization subproblems for a set of independent linear fractional transformation (LFT) systems, whose dimensions are equal to that of a single agent plant plus the associated local IQC dynamics. New delay control synthesis conditions for each subproblem are fully characterized as linear matrix inequalities (LMIs). A numerical example is used to demonstrate the proposed approach.
Sovereignty, Indigeneity, and Biopower: The Carceral Trajectories of Canada's Forced Removals of Indigenous Children and the Contemporary Prison System
Authors: MacDonald David , Gillis Jacqueline
Published: December 2017

For seven generations, the Canadian settler state sought to take Indigenous children from their parents and home communities, to a network of residential schools, where the goal of the state and the four main Christians churches was to destroy all that was Indigenous in these children. A key purpose was to make Indigenous peoples, alongside their sovereign rights to land, language, spirituality, and governance disappear. As this system wound down, forcible transfer shifted to forcing Indigenous children into foster and institutional “care”, a process known as the “60s scoop”. These forms of child incarceration have a link to extremely high rates of Indigenous imprisonment in Canada’s settler colonial justice system. In this article we deploy a modified Foucauldian understanding of carceral politics to explore the history and intent behind the IRS system, the 60s scoop, and the prison system in Canada.
Free-standing hydrogel-particle composite membrane with dynamically controlled permeability
Authors: Sergelen Khulan , Petri Christian , Jonas Ulrich , Dostalek Jakub
Published: December 2017

The preparation and investigation of a free-standing membrane made from a composite of thermoresponsive poly(N-isopropylacrylamide) (pNIPAAm) and polystyrene nanoparticles (PS NP) with temperature-controlled permeability is reported. The method exploits the light-induced crosslinking of the photo-reactive pNIPAAm-based polymer and mechanical reinforcement of the membrane structure by the polystyrene nanoparticles. About micrometer thick layers were either directly attached to a gold surface or prepared as free-standing layers spanning over arrays of microfluidic channels with a width of about hundred microns by using template stripping. Diffusion of liquid medium, low molecular weight molecules, and large molecular weight proteins contained in blood through the composite membrane was observed with combined surface plasmon resonance (SPR) and optical waveguide spectroscopy (OWS). The swelling ratio, permeability, and nonspecific sorption to these composite membranes were investigated by SPR and OWS as a function of molecular weight of analyte, loading of PS NP in the composite film, and temperature. The authors show successful preparation of a defect-free membrane structure that acts as a thermoresponsive filter with nanoscale pores spanning over an area of several square millimeters. This membrane can be reversibly switched to block or allow the diffusion of low mass molecules to the sensor surface by temperature-triggered swelling and collapsing of the hydrogel component. Blocking of diffusion and low unspecific sorption of proteins contained in blood serum is observed. These features make this platform interesting for potential future applications in continuous monitoring biosensors for the analysis of low molecular weight drug analytes or for advanced cell-on-chip microfluidic studies.
PPARδ activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis
Authors: Dickey Audrey S. , Sanchez Dafne N. , Arreola Martin , Sampat Kunal R. , Fan Weiwei , Arbez Nicolas , Akimov Sergey , Van Kanegan Michael J. , Ohnishi Kohta , Gilmore-Hall Stephen K. , Flores April L. , Nguyen Janice M. , Lomas Nicole , Hsu Cynthia L. , Lo Donald C. , Ross Christopher A. , Masliah Eliezer , Evans Ronald M. , La Spada Albert R.
Published: December 2017

PPARδ activation by bexarotene in a mouse model of Huntington’s disease rescues defective oxidative metabolism and is neuroprotective.
A degradation fragment of type X collagen is a real-time marker for bone growth velocity
Authors: Coghlan Ryan F. , Oberdorf Jon A. , Sienko Susan , Aiona Michael D. , Boston Bruce A. , Connelly Kara J. , Bahney Chelsea , LaRouche Jeremie , Almubarak Sarah M. , Coleman Daniel T. , Girkontaite Irute , von der Mark Klaus , Lunstrum Gregory P. , Horton William A.
Published: December 2017

A type X collagen fragment derived from endochondral ossification and detected in blood is a marker for growth velocity.
A randomized controlled safety/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection
Authors: Sneller Michael C. , Justement J. Shawn , Gittens Kathleen R. , Petrone Mary E. , Clarridge Katherine E. , Proschan Michael A. , Kwan Richard , Shi Victoria , Blazkova Jana , Refsland Eric W. , Morris Daryl E. , Cohen Kristen W. , McElrath M. Juliana , Xu Rong , Egan Michael A. , Eldridge John H. , Benko Erika , Kovacs Colin , Moir Susan , Chun Tae-Wook , Fauci Anthony S.
Published: December 2017

Despite lack of vaccine efficacy, the kinetics and magnitude of HIV rebound in early-treated patients affect future clinical trial design.
Rapid Microarray-Based Detection of Rifampin, Isoniazid, and Fluoroquinolone Resistance in Mycobacterium tuberculosis by Use of a Single Cartridge
Authors: Havlicek Juliane , Dachsel Beatrice , Slickers Peter , Andres Sönke , Beckert Patrick , Feuerriegel Silke , Niemann Stefan , Merker Matthias , Labugger Ines
Published: December 2017

The rapid and robust identification of mutations in
Mycobacterium tuberculosis
complex (MTBC) strains mediating multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes is crucial to combating the MDR tuberculosis (TB) epidemic. Currently available molecular anti-TB drug susceptibility tests either are restricted to a single target or drug (i.e., the Xpert MTB/RIF test) or present a risk of cross-contamination due to the design limitations of the open platform (i.e., line probe assays). With a good understanding of the technical and commercial boundaries, we designed a test cartridge based on an oligonucleotide array into which dried reagents are introduced and which has the ability to identify MTBC strains resistant to isoniazid, rifampin, and the fluoroquinolones. The melting curve assay interrogates 43 different mutations in the rifampin resistance-determining region (RRDR) of
rpoB
,
rpoB
codon 572,
katG
codon 315, the
inhA
promoter region, and the quinolone resistance-determining region (QRDR) of
gyrA
in a closed cartridge system within 90 min. Assay performance was evaluated with 265 clinical MTBC isolates, including MDR/XDR, non-MDR, and fully susceptible isolates, from a drug resistance survey performed in Swaziland in 2009 and 2010. In 99.5% of the cases, the results were consistent with data previously acquired utilizing Sanger sequencing. The assay, which uses a closed cartridge system in combination with a battery-powered Alere q analyzer and which has the potential to extend the current gene target panel, could serve as a rapid and robust point-of-care test in settings lacking a comprehensive molecular laboratory infrastructure to differentiate TB patients infected with MDR and non-MDR strains and to assist clinicians with their early treatment decisions.
Multicenter Evaluation of the ePlex Respiratory Pathogen Panel for the Detection of Viral and Bacterial Respiratory Tract Pathogens in Nasopharyngeal Swabs
Authors: Babady N. Esther , England Matthew R. , Jurcic Smith Kristen L. , He Taojun , Wijetunge Dona Saumya , Tang Yi-Wei , Chamberland Robin R. , Menegus Marilyn , Swierkosz Ella M. , Jerris Robert C. , Greene Wallace
Published: December 2017

The performance of the new ePlex Respiratory Pathogen (RP) panel (GenMark Diagnostics) for the simultaneous detection of 19 viruses (influenza A virus; influenza A H1 virus; influenza A 2009 H1 virus; influenza A H3 virus; influenza B virus; adenovirus; coronaviruses [HKU1, OC43, NL63, and 229E]; human rhinovirus/enterovirus; human metapneumovirus; parainfluenza viruses 1, 2, 3, and 4; and respiratory syncytial virus [RSV] [RSV subtype A and RSV subtype B]) and 2 bacteria (
Mycoplasma pneumoniae
and
Chlamydia pneumoniae
) was evaluated. Prospectively and retrospectively collected nasopharyngeal swab (NPS) specimens (
n
= 2,908) were evaluated by using the ePlex RP panel, with the bioMérieux/BioFire FilmArray Respiratory Panel (BioFire RP) as the comparator method. Discordance analysis was performed by using target-specific PCRs and bidirectional sequencing. The reproducibility of the assay was evaluated by using reproducibility panels comprised of 6 pathogens. The overall agreement between the ePlex RP and BioFire RP results was >95% for all targets. Positive percent agreement with the BioFire RP result for viruses ranged from 85.1% (95% confidence interval [CI], 80.2% to 88.9%) to 95.1% (95% CI, 89.0% to 97.9%), while negative percent agreement values ranged from 99.5% (95% CI, 99.1% to 99.7%) to 99.8% (95% CI, 99.5% to 99.9%). Additional testing of discordant targets (12%; 349/2,908) confirmed the results of ePlex RP for 38% (131/349) of samples tested. Reproducibility was 100% for all targets tested, with the exception of adenovirus, for which reproducibilities were 91.6% at low virus concentrations and 100% at moderate virus concentrations. The ePlex RP panel offers a new, rapid, and sensitive “sample-to-answer” multiplex panel for the detection of the most common viral and bacterial respiratory pathogens.
The Heptad Repeat C Domain of the Respiratory Syncytial Virus Fusion Protein Plays a Key Role in Membrane Fusion
Authors: Bermingham Imogen M. , Chappell Keith J. , Watterson Daniel , Young Paul R.
Published: December 2017

Respiratory syncytial virus (RSV) mediates host cell entry through the fusion (F) protein, which undergoes a conformational change to facilitate the merger of viral and host lipid membrane envelopes. The RSV F protein comprises a trimer of disulfide-bonded F
1
and F
2
subunits that is present on the virion surface in a metastable prefusion state. This prefusion form is readily triggered to undergo refolding to bring two heptad repeats (heptad repeat A [HRA] and HRB) into close proximity to form a six-helix bundle that stabilizes the postfusion form and provides the free energy required for membrane fusion. This process can be triggered independently of other proteins. Here, we have performed a comprehensive analysis of a third heptad repeat region, HRC (amino acids 75 to 97), an amphipathic α-helix that lies at the interface of the prefusion F trimer and is a major structural feature of the F
2
subunit. We performed alanine scanning mutagenesis from Lys-75 to Met-97 and assessed all mutations in transient cell culture for expression, proteolytic processing, cell surface localization, protein conformation, and membrane fusion. Functional characterization revealed a striking distribution of activity in which fusion-increasing mutations localized to one side of the helical face, while fusion-decreasing mutations clustered on the opposing face. Here, we propose a model in which HRC plays a stabilizing role within the globular head for the prefusion F trimer and is potentially involved in the early events of triggering, prompting fusion peptide release and transition into the postfusion state.

IMPORTANCE
RSV is recognized as the most important viral pathogen among pediatric populations worldwide, yet no vaccine or widely available therapeutic treatment is available. The F protein is critical for the viral replication process and is the major target for neutralizing antibodies. Recent years have seen the development of prefusion stabilized F protein-based approaches to vaccine design. A detailed understanding of the specific domains and residues that contribute to protein stability and fusion function is fundamental to such efforts. Here, we present a comprehensive mutagenesis-based study of a region of the RSV F
2
subunit (amino acids 75 to 97), referred to as HRC, and propose a role for this helical region in maintaining the delicate stability of the prefusion form.
The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers
Authors: Newman Joseph , Asfor Amin S. , Berryman Stephen , Jackson Terry , Curry Stephen , Tuthill Tobias J.
Published: December 2017

Productive picornavirus infection requires the hijacking of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein, and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerization of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and posttranslational modification of the capsid precursor (P1-2A) by viral and cellular enzymes and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90) impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titer by more than 10-fold while not affecting the activity of a subgenomic replicon, indicating that translation and replication of viral RNA were unaffected by the drug.

IMPORTANCE
FMDV of the
Picornaviridae
family is a pathogen of huge economic importance to the livestock industry due to its effect on the restriction of livestock movement and necessary control measures required following an outbreak. The study of FMDV capsid assembly, and picornavirus capsid assembly more generally, has tended to be focused upon the formation of capsids from pentameric intermediates or the immediate cotranslational modification of the capsid precursor protein. Here, we describe a system to analyze the early stages of FMDV pentameric capsid intermediate assembly and demonstrate a novel requirement for the cellular chaperone hsp90 in the formation of these pentameric intermediates. We show the added complexity involved for this process to occur, which could be the basis for a novel antiviral control mechanism for FMDV.
Nucleic Acid Polymers Are Active against Hepatitis Delta Virus InfectionIn Vitro
Authors: Beilstein Frauke , Blanchet Matthieu , Vaillant Andrew , Sureau Camille
Published: December 2017

In this study, anin vitroinfection model for the hepatitis delta virus (HDV) was used to evaluate the antiviral effects of phosphorothioate nucleic acid polymers (NAPs) and investigate their mechanism of action. The results show that NAPs inhibit HDV infection at concentrations less than 4 μM in cultures of differentiated human hepatoma cells. NAPs were shown to be active at viral entry but inactive postentry on HDV RNA replication. Inhibition was independent of the NAP nucleotide sequence but dependent on both size and amphipathicity of the polymer. NAP antiviral activity was effective against HDV virions bearing the main hepatitis B virus (HBV) immune escape substitutions (D144A and G145R) and was pangenomic with regard to HBV envelope proteins. Furthermore, similar to immobilized heparin, immobilized NAPs could bind HDV particles, suggesting that entry inhibition was due, at least in part, to preventing attachment of the virus to cell surface glycosaminoglycans. The results document NAPs as a novel class of antiviral compounds that can prevent HDV propagation.

IMPORTANCEHDV infection causes the most severe form of viral hepatitis in humans and one of the most difficult to cure. Currently, treatments are limited to long-term administration of interferon at high doses, which provide only partial efficacy. There is thus an urgent need for innovative approaches to identify new antiviral against HDV. The significance of our study is in demonstrating that nucleic acid polymers (NAPs) are active against HDV by targeting the envelope of HDV virions. In anin vitroinfection assay, NAP activity was recorded at concentrations less than 4 μM in the absence of cell toxicity. Furthermore, the fact that NAPs could block HDV at viral entry suggests their potential to control the spread of HDV in a chronically HBV-infected liver. In addition, NAP anti-HDV activity was pangenomic with regard to HBV envelope proteins and not circumvented by HBsAg substitutions associated with HBV immune escape.
Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection
Authors: Iwatsuki-Horimoto Kiyoko , Nakajima Noriko , Ichiko Yurie , Sakai-Tagawa Yuko , Noda Takeshi , Hasegawa Hideki , Kawaoka Yoshihiro
Published: December 2017

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies.

IMPORTANCE
We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses.
Novel Sulfolobus Virus with an Exceptional Capsid Architecture
Authors: Wang Haina , Guo Zhenqian , Feng Hongli , Chen Yufei , Chen Xiuqiang , Li Zhimeng , Hernández-Ascencio Walter , Dai Xin , Zhang Zhenfeng , Zheng Xiaowei , Mora-López Marielos , Fu Yu , Zhang Chuanlun , Zhu Ping , Huang Li
Published: December 2017

A novel archaeal virus, denoted
Sulfolobus ellipsoid virus 1
(SEV1), was isolated from an acidic hot spring in Costa Rica. The morphologically unique virion of SEV1 contains a protein capsid with 16 regularly spaced striations and an 11-nm-thick envelope. The capsid exhibits an unusual architecture in which the viral DNA, probably in the form of a nucleoprotein filament, wraps around the longitudinal axis of the virion in a plane to form a multilayered disk-like structure with a central hole, and 16 of these structures are stacked to generate a spool-like capsid. SEV1 harbors a linear double-stranded DNA genome of ∼23 kb, which encodes 38 predicted open reading frames (ORFs). Among the few ORFs with a putative function is a gene encoding a protein-primed DNA polymerase. Sixfold symmetrical virus-associated pyramids (VAPs) appear on the surface of the SEV1-infected cells, which are ruptured to allow the formation of a hexagonal opening and subsequent release of the progeny virus particles. Notably, the SEV1 virions acquire the lipid membrane in the cytoplasm of the host cell. The lipid composition of the viral envelope correlates with that of the cell membrane. These results suggest the use of a unique mechanism by SEV1 in membrane biogenesis.

IMPORTANCE
Investigation of archaeal viruses has greatly expanded our knowledge of the virosphere and its role in the evolution of life. Here we show that
Sulfolobus ellipsoid virus 1
(SEV1), an archaeal virus isolated from a hot spring in Costa Rica, exhibits a novel viral shape and an unusual capsid architecture. The SEV1 DNA wraps multiple times in a plane around the longitudinal axis of the virion to form a disk-like structure, and 16 of these structures are stacked to generate a spool-like capsid. The virus acquires its envelope intracellularly and exits the host cell by creating a hexagonal hole on the host cell surface. These results shed significant light on the diversity of viral morphogenesis.