bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Efficacy of a Single Progesterone Determination to Assess Full‐Term Pregnancy in the Bitch
Authors: Rota A , Charles C , Starvaggi Cucuzza A , Pregel P
Published: October 2015

Contents

In clinical settings, when the reproductive history of a near‐term bitch is limited to mating dates, the possibility to accurately assess whether pregnancy is at term could be very useful in order to be able to plan a correct management of parturition or to safely perform an elective Caesarean section. The aim of this study was to assess the diagnostic efficacy of a single progesterone determination, measured by chemiluminescent immunoassay (CLIA), in predicting the occurrence of parturition on the following day. At least one blood sample was collected from 51 pre‐partum bitches during the 3 days before parturition and on day of parturition. The efficacy of progesterone as a marker of the end of pregnancy was tested using a receiver operating characteristic (ROC) analysis. Youden's index was calculated to select the optimal cut‐off value (with 95% confidence interval), aiming at maximizing the correct identification of negative events, so not to risk to diagnose as full term a bitch which is not. Progesterone concentration lower than 3.4 ng/ml correctly identified the bitches whelping the following day; however, because of the obliged prudential approach, sensitivity was low (46.88%), and 17 of 32 full‐term bitches were missed. Due to a very large individual variation, a single progesterone determination has low diagnostic efficacy, although it can represent a useful first screening.
Chemical and physical weathering in a hot‐arid, tectonically active alluvial system of Anza Borrego Desert, California
Authors: Joo Young Ji , Elwood Madden Megan E. , Soreghan Gerilyn S.
Published: October 2015

Investigation of chemical and physical weathering of bedrock and alluvial sediment in the Anza Borrego Desert, California, sheds light on weathering processes in hot‐arid systems and clarifies interpretations of climate from alluvial sediment. All of the alluvial sediment in the study area emanates from Cretaceous tonalite of the Peninsular Range, enabling exploration of the effects of external variables – climate, transport distance and tectonics – on the physical and chemical properties of the sediment. Chemical weathering in this area is dominated by plagioclase alteration observed in both bedrock outcrops and sediment, evinced most clearly by changes in the Eu anomaly. Biotite chemical weathering, manifested by interlayer K+ loss, is not evident in bedrock, but clearly observed in the sediment. Despite the weak intensity of chemical weathering (Chemical Index of Alteration = 56 to 62), fine‐grained (<63 μm) sediment displays a clear weathering trend in A–CN–K space and contains up to 25% clay minerals. Physical abrasion and grain‐size reduction in biotite during transport predominates in the sediment, whereas physical (insolation) weathering affecting bedrock is inferred from estimates of differential thermal expansion of mineral phases in response to extreme temperature changes in the study area. Chemical alteration and Brunauer–Emmett–Teller surface area both increase within the active Elsinore fault zone at the distal end of the depositional transect, reflecting tectonic‐induced fracturing and associated accelerated weathering. Extensive fracturing, together with a more humid Pleistocene climate, probably facilitated in situ bedrock weathering, preceding arid alluvial deposition in the Holocene. This study demonstrates that both climate and tectonic processes can affect chemical and physical weathering, resulting in alteration of plagioclase, leaching of K+ from biotite in the sediment and formation of clay minerals, even in hot, arid systems.
Mobility and emplacement in north coast Papua New Guinea: Worlding the Pacific Marine Industrial Zone
Authors: Stead Victoria
Published: October 2015

On the north coast of Papua New Guinea, the construction of the Pacific Marine Industrial Zone is catalysing movements of people, capital and things, as well as of the ideas and imaginings which accompany and make them meaningful. Drawn from literary and postcolonial studies, the concept ofworldingoffers a narrative framework through which to think through these movements and the ways in which they complicate prevailing narratives of globalisation. At the Pacific Marine Industrial Zone, the neoliberal worldings that inform the project do not simply catalyse movements, but also act to impose barriers to movement. Local communities assert connection to place, but also generate new circuits of mobility, and rearticulate ideas ofkastom(custom) that have movement at their core. An emphasis onworlding—drawing particularly on Heidegger's distinction between world and earth—allows for a more complex reflection on the relationship between mobility and emplacement, one that more fully illuminates the complexity of the relationship itself, and the way it is experienced at thePMIZsite.
Coastal lagoons and beach ridges as complementary sedimentary archives for the reconstruction of Holocene relative sea‐level changes
Authors: Sander Lasse , Hede Mikkel U. , Fruergaard Mikkel , Nielsen Lars , Clemmensen Lars B. , Kroon Aart , Johannessen Peter N. , Nielsen Lars H. , Pejrup Morten
Published: October 2015

Coastal lagoons and beach ridges are genetically independent, though non‐continuous, sedimentary archives. We here combine the results from two recently published studies in order to produce an 8000‐year‐long record of Holocene relative sea‐level changes on the island of Samsø, southern Kattegat, Denmark. The reconstruction of the initial mid‐Holocene sea‐level rise is based on the sedimentary infill from topography‐confined coastal lagoons (Sander et al., Boreas, 2015b). Sea‐level index points over the mid‐ to late Holocene period of sea‐level stability and fall are retrieved from the internal structures of a wide beach‐ridge system (Hede et al., The Holocene, 2015). Data from sediment coring, georadar and absolute dating are thus combined in an inter‐disciplinary approach that is highly reproducible in micro‐tidal environments characterised by high sediment supply. We show here that the commonly proximate occurrence of coastal lagoons and beach ridges allows us to produce seamless time series of relative sea‐level changes from field sites in SW Scandinavia and in similar coastal environments.
Formation of a Prismatic Dislocation Loop in the Interface of a Circular Cylindrical Inclusion Embedded in a Thin Slab
Authors: Colin Jérôme
Published: October 2015

The introduction of a prismatic dislocation loop in the interface of an axisymmetric precipitate embedded in a thin slab of infinite lateral extension has been theoretically investigated. The critical misfit strain resulting from the lattice mismatch between the inclusion and the slab has been characterized for the loop formation versus the thickness of the slab and the radius of the inclusion. The case where the precipitate is embedded in a semi-infinite matrix is also discussed and a stability diagram of the structure is displayed with respect to the loop introduction versus the geometric and misfit parameters.
The perception of complex pitch in cochlear implants: A comparison of monopolar and tripolar stimulation
Authors: Fielden Claire A. , Kluk Karolina , Boyle Patrick J. , McKay Colette M.
Published: October 2015

Cochlear implant listeners typically perform poorly in tasks of complex pitch perception (e.g., musical pitch and voice pitch). One explanation is that wide current spread during implant activation creates channel interactions that may interfere with perception of temporal fundamental frequency information contained in the amplitude modulations within channels. Current focusing using a tripolar mode of stimulation has been proposed as a way of reducing channel interactions, minimising spread of excitation and potentially improving place and temporal pitch cues. The present study evaluated the effect of mode in a group of cochlear implant listeners on a pitch ranking task using male and female singing voices separated by either a half or a quarter octave. Results were variable across participants, but on average, pitch ranking was at chance level when the pitches were a quarter octave apart and improved when the difference was a half octave. No advantage was observed for tripolar over monopolar mode at either pitch interval, suggesting that previously published psychophysical advantages for focused modes may not translate into improvements in complex pitch ranking. Evaluation of the spectral centroid of the stimulation pattern, plus a lack of significant difference between male and female voices, suggested that participants may have had difficulty in accessing temporal pitch cues in either mode.
Lifelong memories may reside in nets around brain cells
Authors: Underwood Emily
Published: October 2015

Studies suggest key role for perineuronal networks of proteins and sugars in long-term memory.
Crisis manager with 194 bosses
Authors: Kupferschmidt Kai
Published: October 2015

WHO Director-General Margaret Chan wants member countries to put their money where their mouths are.
Miocene small-bodied ape from Eurasia sheds light on hominoid evolution
Authors: Alba David M. , Almécija Sergio , DeMiguel Daniel , Fortuny Josep , de los Ríos Miriam Pérez , Pina Marta , Robles Josep M. , Moyà-Solà Salvador
Published: October 2015

Meet your gibbon cousin

Apes are divided into two groups: larger-bodied apes, or hominoids, such as humans, chimps, and gorillas; and smaller-bodied hylobatids, such as gibbons. These two lineages are thought to have diverged rather cleanly, sharing few similarities after the emergence of crown hominoids. Alba
et al.
describe a new ape from the Miocene era that contains characteristics from both hominoids and small-bodied apes (see the Perspective by Benefit and McCrossin). Thus, early small-bodied apes may have contributed more to the evolution of the hominoid lineage than previously assumed.

Science
, this issue p.
10.1126/science.aab2625
; see also p.
515
Disease tolerance mediated by microbiome
E. coli
involves inflammasome and IGF-1 signaling
Authors: Schieber Alexandria M. Palaferri , Lee Yujung Michelle , Chang Max W. , Leblanc Mathias , Collins Brett , Downes Michael , Evans Ronald M. , Ayres Janelle S.
Published: October 2015

The benefits of
Escherichia coli

Infection and intestinal damage can trigger severe muscle wasting and loss of fat in mice. How this happens is poorly understood. Palaferri Schieber
et al.
discovered a protective
Escherichia coli
strain in their mouse colony. Mice intestinally colonized with the
E. coli
and infected with the food-poisoning bug
Salmonella
or with the lung pathogen
Burkholderia
did not waste away. Without the
E. coli
, similarly infected mice became fatally ill. The protective
E. coli
stimulated an innate immune mechanism that ensured that muscle-signaling pathways were not damaged by infection. Thus, the friendly
E. coli
allowed its host to tolerate and survive the pathogens.

Science
, this issue p.
558
Cycling Li-O
2
batteries via LiOH formation and decomposition
Authors: Liu Tao , Leskes Michal , Yu Wanjing , Moore Amy J. , Zhou Lina , Bayley Paul M. , Kim Gunwoo , Grey Clare P.
Published: October 2015

Solving the problems with Li-air batteries

Li-air batteries come as close as possible to the theoretical limits for energy density in a battery. By weight, this is roughly 10 times higher than conventional lithium-ion batteries and would be sufficient to power cars with a range comparable to those with gasoline engines. But engineering a Li-air battery has been a challenge. Liu
et al.
managed to overcome the remaining challenges: They were able to avoid electrode passivation, turn limited solvent stability into an advantage, eliminate the fatal problems caused by superoxides, achieve high power with negligible degradation, and even circumvent the problems of removing atmospheric water.

Science
, this issue p.
530
Mobile metallic domain walls in an all-in-all-out magnetic insulator
Authors: Ma Eric Yue , Cui Yong-Tao , Ueda Kentaro , Tang Shujie , Chen Kai , Tamura Nobumichi , Wu Phillip M. , Fujioka Jun , Tokura Yoshinori , Shen Zhi-Xun
Published: October 2015

Visualizing conducting domain walls

When a metal undergoes a phase transition and becomes insulating, it sometimes also becomes magnetically ordered. It is possible that some metallicity survives along the boundaries of magnetic domains, the so-called domain walls, but the question is difficult to address directly in experiments. Ma
et al.
did just that by mapping out the conductance of the material Nd
2
Ir
2
O
7
in its low-temperature magnetic insulating phase, using microwave impedance microscopy. The magnetic domain walls showed up clearly in the images as regions of high conductance.

Science
, this issue p.
538
A unified initiative to harness Earth's microbiomes
Authors: Alivisatos A. P. , Blaser M. J. , Brodie E. L. , Chun M. , Dangl J. L. , Donohue T. J. , Dorrestein P. C. , Gilbert J. A. , Green J. L. , Jansson J. K. , Knight R. , Maxon M. E. , McFall-Ngai M. J. , Miller J. F. , Pollard K. S. , Ruby E. G. , Taha S. A. ,   Unified Microbiome Initiative Consortium
Published: October 2015

Transition from description to causality and engineering
A window into ape evolution
Authors: Benefit Brenda R. , McCrossin Monte L.
Published: October 2015

A fossil of an ape ancestor helps to explain gibbon evolution

[Also see Report by

Alba
et al.

]
Randomness rules
Authors: Markovic Nina
Published: October 2015

Disorder can have dramatic effects on quantum transitions

[Also see Report by

Xing
et al.

]
Naturally Acquired HMW1- and HMW2-Specific Serum Antibodies in Adults and Children Mediate Opsonophagocytic Killing of Nontypeable Haemophilus influenzae
Authors: Winter Linda E. , Barenkamp Stephen J.
Published: October 2015

The HMW1 and HMW2 proteins are highly immunogenic adhesins expressed by approximately 75% of nontypeableHaemophilus influenzae(NTHi) strains, and HMW1- and HMW2-specific antibodies can mediate opsonophagocytic killing of NTHi. In this study, we assessed the ability of HMW1- and HMW2-specific antibodies in sera from healthy adults and convalescent-phase sera from children with NTHi otitis media to mediate killing of homologous and heterologous NTHi. The serum samples were examined pre- and postadsorption on HMW1 and HMW2 affinity columns, and affinity-purified antibodies were assessed for ability to mediate killing of homologous and heterologous strains. Adult serum samples mediated the killing of six prototype NTHi strains at titers of <1:10 to 1:1,280. HMW1- and HMW2-adsorbed sera demonstrated unchanged to 8-fold decreased opsonophagocytic titers against the homologous strains. Each affinity-purified antibody preparation mediated the killing of the respective homologous strain at titers of <1:10 to 1:320 and of the five heterologous strains at titers of <1:10 to 1:320, with most preparations killing most heterologous strains to some degree. None of the acute-phase serum samples from children mediated killing, but each convalescent-phase serum sample mediated killing of the infecting strain at titers of 1:40 to 1:640. HMW1- and HMW2-adsorbed convalescent-phase serum samples demonstrated ≥4-fold decreases in titer. Three of four affinity-purified antibody preparations mediated killing of the infecting strain at titers of 1:20 to 1:320, but no killing of representative heterologous strains was observed. HMW1- and HMW2-specific antibodies capable of mediating opsonophagocytic killing are present in the serum from normal adults and develop in convalescent-phase sera of children with NTHi otitis media. Continued investigation of the HMW1 and HMW2 proteins as potential vaccine candidates for the prevention of NTHi disease is warranted.
Enumeration of Gut-Homing β7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique
Authors: Bhuiyan Taufiqur Rahman , Hoq Mohammad Rubel , Nishat Naoshin Sharmin , Al Mahbuba Deena , Rashu Rasheduzzaman , Islam Kamrul , Hossain Lazina , Dey Ayan , Harris Jason B. , Ryan Edward T. , Calderwood Stephen B. , Svennerholm Ann-Mari , Qadri Firdausi
Published: October 2015

Vibrio choleraeand enterotoxigenicEscherichia coli(ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates β7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. β7 is a cell surface marker associated with mucosal homing. We isolated β7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination.
Meningitis and Bacteremia Due to Neisseria cinerea following a Percutaneous Rhizotomy of the Trigeminal Ganglion
Authors: von Kietzell M. , Richter H. , Bruderer T. , Goldenberger D. , Emonet S. , Strahm C.
Published: October 2015

Neisseria cinerea
is a human commensal. The first known case of meningitis and bacteremia due to
Neisseria cinerea
following percutaneous glycerol instillation of the trigeminal ganglion is reported. Conventional phenotypic methods and complete 16S RNA gene sequencing accurately identified the pathogen. Difficulties in differentiation from pathogenic neisseriae are discussed.
An Update on Clostridium difficile Toxinotyping
Authors: Rupnik Maja , Janezic Sandra
Published: October 2015

Toxinotyping is a PCR-restriction fragment length polymorphism (RFLP)-based method for differentiation of
Clostridium difficile
strains according to the changes in the pathogenicity locus (PaLoc), a region coding for toxins A and B. Toxinotypes are a heterogenous group of strains that are important in the development of molecular diagnostic tests and vaccines and are a good basis for
C. difficile
phylogenetic studies. Here we describe an overview of the 34 currently known toxinotypes (I to XXXIV) and some changes in nomenclature.
Laboratory-Acquired Infection with Salmonella enterica Serovar Typhimurium Exposed by Whole-Genome Sequencing
Authors: Alexander David C. , Fitzgerald Stephen F. , DePaulo Rachel , Kitzul Rosanne , Daku Dawn , Levett Paul N. , Cameron Andrew D. S.
Published: October 2015

Despite advances in laboratory design, professional training, and workplace biosafety guidelines, laboratory-acquired infections continue to occur. Effective tools are required to investigate cases and prevent future illness. Here, we demonstrate the value of whole-genome sequencing as a tool for the identification and source attribution of laboratory-acquired salmonellosis.
Microbiological Characteristics of Chlamydia trachomatis and Neisseria gonorrhoeae Infections in South African Women
Authors: Dubbink Jan Henk , de Waaij Dewi J. , Bos Myrte , van der Eem Lisette , Bébéar Cécile , Mbambazela Nontembeko , Ouburg Sander , Peters Remco P. H. , Morré Servaas A.
Published: October 2015

We analyzed data of 263 women with at least one genital or anorectal sexually transmitted infection from a cross-sectional study conducted in rural South Africa. We provide new insights concerning the concurrence of
Chlamydia trachomatis
,
Neisseria gonorrhoeae
,
Mycoplasma genitalium
, and
Trichomonas vaginalis
infections as well as the characteristics of bacterial loads.
Elucidation of the Molecular Mechanism Driving Duplication of the HIV-1 PTAP Late Domain
Authors: Martins Angelica N. , Waheed Abdul A. , Ablan Sherimay D. , Huang Wei , Newton Alicia , Petropoulos Christos J. , Brindeiro Rodrigo D. M. , Freed Eric O.
Published: October 2015

HIV-1 uses cellular machinery to bud from infected cells. This cellular machinery is comprised of several multiprotein complexes known as endosomal sorting complexes required for transport (ESCRTs). A conserved late domain motif, Pro-Thr-Ala-Pro (PTAP), located in the p6 region of Gag (p6Gag), plays a central role in ESCRT recruitment to the site of virus budding. Previous studies have demonstrated that PTAP duplications are selected in HIV-1-infected patients during antiretroviral therapy; however, the consequences of these duplications for HIV-1 biology and drug resistance are unclear. To address these questions, we constructed viruses carrying a patient-derived PTAP duplication with and without drug resistance mutations in the viral protease. We evaluated the effect of the PTAP duplication on viral release efficiency, viral infectivity, replication capacity, drug susceptibility, and Gag processing. In the presence of protease inhibitors, we observed that the PTAP duplication in p6Gagsignificantly increased the infectivity and replication capacity of the virus compared to those of viruses bearing only resistance mutations in protease. Our biochemical analysis showed that the PTAP duplication, in combination with mutations in protease, enhances processing between the nucleocapsid and p6 domains of Gag, resulting in more complete Gag cleavage in the presence of protease inhibitors. These results demonstrate that duplication of the PTAP motif in p6Gagconfers a selective advantage in viral replication by increasing Gag processing efficiency in the context of protease inhibitor treatment, thereby enhancing the drug resistance of the virus. These findings highlight the interconnected role of PTAP duplications and protease mutations in the development of resistance to antiretroviral therapy.

IMPORTANCEResistance to current drug therapy limits treatment options in many HIV-1-infected patients. Duplications in a Pro-Thr-Ala-Pro (PTAP) motif in the p6 domain of Gag are frequently observed in viruses derived from patients on protease inhibitor (PI) therapy. However, the reason that these duplications arise and their consequences for virus replication remain to be established. In this study, we examined the effect of PTAP duplication on PI resistance in the context of wild-type protease or protease bearing PI resistance mutations. We observe that PTAP duplication markedly enhances resistance to a panel of PIs. Biochemical analysis reveals that the PTAP duplication reverses a Gag processing defect imposed by the PI resistance mutations in the context of PI treatment. The results provide a long-sought explanation for why PTAP duplications arise in PI-treated patients.
Dengue Virus prM-Specific Human Monoclonal Antibodies with Virus Replication-Enhancing Properties Recognize a Single Immunodominant Antigenic Site
Authors: Smith Scott A. , Nivarthi Usha K. , de Alwis Ruklanthi , Kose Nurgun , Sapparapu Gopal , Bombardi Robin , Kahle Kristen M. , Pfaff Jennifer M. , Lieberman Sherri , Doranz Benjamin J. , de Silva Aravinda M. , Crowe James E.
Published: October 2015

The proposed antibody-dependent enhancement (ADE) mechanism for severe dengue virus (DENV) disease suggests that non-neutralizing serotype cross-reactive antibodies generated during a primary infection facilitate entry into Fc receptor bearing cells during secondary infection, resulting in enhanced viral replication and severe disease. One group of cross-reactive antibodies that contributes considerably to this serum profile target the premembrane (prM) protein. We report here the isolation of a large panel of naturally occurring human monoclonal antibodies (MAbs) obtained from subjects following primary DENV serotype 1, 2, or 3 or secondary natural DENV infections or following primary DENV serotype 1 live attenuated virus vaccination to determine the antigenic landscape on the prM protein that is recognized by human antibodies. We isolated 25 prM-reactive human MAbs, encoded by diverse antibody-variable genes. Competition-binding studies revealed that all of the antibodies bound to a single major antigenic site on prM. Alanine scanning-based shotgun mutagenesis epitope mapping studies revealed diverse patterns of fine specificity of various clones, suggesting that different antibodies use varied binding poses to recognize several overlapping epitopes within the immunodominant site. Several of the antibodies interacted with epitopes on both prM and E protein residues. Despite the diverse genetic origins of the antibodies and differences in the fine specificity of their epitopes, each of these prM-reactive antibodies was capable of enhancing the DENV infection of Fc receptor-bearing cells.

IMPORTANCE
Antibodies may play a critical role in the pathogenesis of enhanced DENV infection and disease during secondary infections. A substantial proportion of enhancing antibodies generated in response to natural dengue infection are directed toward the prM protein. The fine specificity of human prM antibodies is not understood. Here, we isolated a panel of dengue prM-specific human monoclonal antibodies from individuals after infection in order to define the mode of molecular recognition by enhancing antibodies. We found that only a single antibody molecule can be bound to each prM protein at any given time. Distinct overlapping epitopes were mapped, but all of the epitopes lie within a single major antigenic site, suggesting that this antigenic domain forms an immunodominant region of the protein. Neutralization and antibody-dependent enhanced replication experiments showed that recognition of any of the epitopes within the major antigenic site on prM was sufficient to cause enhanced infection of target cells.
Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus
Authors: Silvas Jesus A. , Popov Vsevolod L. , Paulucci-Holthauzen Adriana , Aguilar Patricia V.
Published: October 2015

Severe fever with thrombocytopenia syndrome (SFTS) virus is a newly recognized member of the genus
Phlebovirus
in the family
Bunyaviridae
. The virus was isolated from patients presenting with hemorrhagic manifestations and an initial case fatality rate of 12 to 30% was reported. Due to the recent emergence of this pathogen, there is limited knowledge on the molecular virology of SFTS virus. Recently, we reported that the SFTS virus NSs protein inhibited the activation of the beta interferon (IFN-β) promoter. Furthermore, we also found that SFTS virus NSs relocalizes key components of the IFN response into NSs-induced cytoplasmic structures. Due to the important role these structures play during SFTS virus replication, we conducted live cell imaging studies to gain further insight into the role and trafficking of these cytoplasmic structures during virus infection. We found that some of the SFTS virus NSs-positive cytoplasmic structures were secreted to the extracellular space and endocytosed by neighboring cells. We also found that these secreted structures isolated from NSs-expressing cells and SFTS virus-infected cells were positive for the viral protein NSs and the host protein CD63, a protein associated with extracellular vesicles. Electron microscopy studies also revealed that the isolated CD63-immunoprecipitated extracellular vesicles produced during SFTS virus infection contained virions. The virions harbored within these structures were efficiently delivered to uninfected cells and were able to sustain SFTS virus replication. Altogether, these results suggest that SFTS virus exploits extracellular vesicles to mediate virus receptor-independent transmission to host cells and open the avenue for novel therapeutic strategies against SFTS virus and related pathogens.

IMPORTANCE
SFTS virus is novel bunyavirus associated with hemorrhagic fever illness. Currently, limited information is available about SFTS virus. In the present study, we demonstrated that extracellular vesicles produced by SFTS virus-infected cells harbor infectious virions. We sought to determine whether these “infectious” extracellular vesicles can mediate transmission of the virus and confirmed that the SFTS virions were efficiently transported by these secreted structures into uninfected cells and were able to sustain efficient replication of SFTS virus. These results have significant impact on our understanding of how the novel tick-borne phleboviruses hijack cellular machineries to establish infection and point toward a novel mechanism for virus replication among arthropod-borne viruses.
Infectious Risks of Air Travel
Authors: Mangili Alexandra , Vindenes Tine , Gendreau Mark
Published: October 2015

Infectious diseases are still among the leading causes of death worldwide due to their persistence, emergence, and reemergence. As the recent Ebola virus disease and MERS-CoV outbreaks demonstrate, the modern epidemics and large-scale infectious outbreaks emerge and spread quickly. Air transportation is a major vehicle for the rapid spread and dissemination of communicable diseases, and there have been a number of reported outbreaks of serious airborne diseases aboard commercial flights including tuberculosis, severe acute respiratory syndrome, influenza, smallpox, and measles, to name a few. In 2014 alone, over 3.3 billion passengers (a number equivalent to 42% of the world population) and 50 million metric tons of cargo traveled by air from 41,000 airports and 50,000 routes worldwide, and significant growth is anticipated, with passenger numbers expected to reach 5.9 billion by 2030. Given the increasing numbers of travelers, the risk of infectious disease transmission during air travel is a significant concern, and this chapter focuses on the current knowledge about transmission of infectious diseases in the context of both transmissions within the aircraft passenger cabin and commercial aircraft serving as vehicles of worldwide infection spread.
The Exosporium Layer of Bacterial Spores: a Connection to the Environment and the Infected Host
Authors: Stewart George C.
Published: October 2015

Much of what we know regarding bacterial spore structure and function has been learned from studies of the genetically well-characterized bacterium
Bacillus subtilis
. Molecular aspects of spore structure, assembly, and function are well defined. However, certain bacteria produce spores with an outer spore layer, the exosporium, which is not present on
B. subtilis
spores. Our understanding of the composition and biological functions of the exosporium layer is much more limited than that of other aspects of the spore. Because the bacterial spore surface is important for the spore's interactions with the environment, as well as being the site of interaction of the spore with the host's innate immune system in the case of spore-forming bacterial pathogens, the exosporium is worthy of continued investigation. Recent exosporium studies have focused largely on members of the
Bacillus cereus
family, principally
Bacillus anthracis
and
Bacillus cereus
. Our understanding of the composition of the exosporium, the pathway of its assembly, and its role in spore biology is now coming into sharper focus. This review expands on a 2007 review of spore surface layers which provided an excellent conceptual framework of exosporium structure and function (A. O. Henriques and C. P. Moran, Jr., Annu Rev Microbiol
61
:555–588, 2007,
http://dx.doi.org/10.1146/annurev.micro.61.080706.093224
). That review began a process of considering outer spore layers as an integrated, multilayered structure rather than simply regarding the outer spore components as independent parts.
Anti-interleukin 6 receptor therapy for hyper-IgD syndrome
Authors: Musters Anne , Tak Paul Peter , Baeten Dominique L P , Tas Sander W
Published: October 2015

Hyper-IgD syndrome (HIDS) is a rare, severe hereditary autoinflammatory disease characterised by periodic fevers, elevated serum IgD levels and a wide range of symptoms. Although a few randomised controlled trials have been performed in this disorder, there are no straightforward treatment protocols and none of the potential therapies are registered for this indication. We report a case of a young woman with severe HIDS who failed numerous therapies. Eventually, rational treatment with a monoclonal anti-interleukin 6 receptor antibody was initiated. This therapy resulted in an impressive clinical improvement and reduction in the number of hospital admissions per year. This case report underlines the difficulty of finding a suitable treatment for rare, severe inflammatory diseases. Furthermore, we show that treating patients with targeted therapies may result in clinical benefit for the patient, as well as simultaneously teach us more about the pathophysiology of these rare, relatively understudied diseases.
Surviving stroke in an Ebola Treatment Centre
Authors: Dhillon Paul , McCarthy Sinead , Gibbs Michael
Published: October 2015

A middle aged woman presented to an Ebola Treatment Centre in West Africa with a 4-day history of fever, fatigue, joint pain and vomiting. She tested positive for Ebola virus disease (EVD) and a standard treatment platform of care was started. On day 3 of her admission, she was found to have suffered a left-sided CVA of unknown aetiology. Treatment was largely supportive within a resource-constrained environment and the added layer of providing care with extensive personal protective equipment, and human resource and safety constraints. The patient was able to clear the EVD and did regain some functional use of her arm and leg. She was discharged on day 15 of her stay, as a survivor of both stroke and Ebola.
Anterior and posterior fixation for delayed treatment of posterior atlantoaxial dislocation without fracture
Authors: Yu Hai Ming , Malhotra Karan , Butler Joseph S , Wu Shi Qiang
Published: October 2015

Posterior atlantoaxial dislocation (PAAD) without fracture of the odontoid process is a rare injury. Authors have variously reported closed or open reduction, followed by either anterior or posterior fixation, but there is no consensus on best treatment. We present a particularly unstable case of PAAD. Open reduction through a retropharyngeal approach with odontoidectomy was required for reduction. Anterior fixation with transarticular lag screws was required prior to posterior fixation with pedicle screws. Despite non-compliance with postoperative immobilisation, imaging at 20-month follow-up confirmed solid fusion. The patient is pain-free with a good range of movement of the neck and has returned to a manual job. Our case had a greater degree of instability than was previously reported, which necessitated 360° fixation. This is the first reported case of this treatment strategy, which provided a very stable fixation allowing fusion despite early movement and without causing undue stiffness.
Embolisation of an iatrogenic pulmonary artery pseudoaneurysm
Authors: Petersen Matthew G , Brinegar Katelyn , Oklu Rahmi
Published: October 2015

A 62-year-old woman with idiopathic cardiomyopathy and class IIIB/stage C heart failure sustained right pulmonary artery injury from a Swan-Ganz catheter during a pretransplant work up. Postprocedure, it was noted that the patient's segmental pulmonary artery catheter was wedged for an unclear period of time. The patient developed a small volume of blood-tinged sputum and a chest CT revealed a 1.3 cm pseudoaneurysm in the right middle lobe medial segment pulmonary artery and a small area of haemorrhage. The patient underwent pulmonary artery preserving coil embolisation of the pseudoaneurysm to prevent further right heart strain, given an ejection fraction of 20%, which resolved haemoptysis. Imaging studies showed preserved distal outflow and no evidence of residual pseudoaneurysm filling.
An observational study to evaluate three pilot programmes of retesting chlamydia-positive individuals within 6 months in the South West of England
Authors: Angel Georgina , Horner Paddy J , O'Brien Norah , Sharp Matt , Pye Karl , Priestley Cecilia , Macleod John , Looker Katharine J , Turner Katherine M E
Published: October 2015

Objectives

To evaluate 3 pilot chlamydia retesting programmes in South West England which were initiated prior to the release of new National Chlamydia Screening Programme (NCSP) guidelines recommending retesting in 2014.

Methods

Individuals testing positive between August 2012 and July 2013 in Bristol (n=346), Cornwall (n=252) and Dorset (n=180) programmes were eligible for inclusion in the retesting pilots. The primary outcomes were retest within 6 months (yes/no) and repeat diagnosis at retest (yes/no), adjusted for area, age and gender.

Results

Overall 303/778 (39.0%) of participants were retested within 6 months and 31/299 (10.4%) were positive at retest. Females were more likely to retest than males and Dorset had higher retesting rates than the other areas.

Conclusions

More than a third of those eligible were retested within the time frame of the study. Chlamydia retesting programmes appear feasible within the context of current programmes to identify individuals at continued risk of infection with relatively low resource and time input.
Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol
Authors: Cluver Catherine A , Walker Susan P , Mol Ben W , Theron Gerard B , Hall David R , Hiscock Richard , Hannan N , Tong S
Published: October 2015

Introduction

Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress.

Methods and analysis

We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies.

Ethics and dissemination

This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals.
Mental health in women 20–23 years after IVF treatment: a Swedish cross-sectional study
Authors: Vikström J , Josefsson A , Bladh M , Sydsjö G
Published: October 2015

Objective

To assess self-perceived mental health in women treated with in vitro fertilisation (IVF) 20–23 years previously, while comparing them to a reference group, and to determine any differences in mental health between those who had given birth, those who had adopted a child, those who had given birth and adopted a child and those who remained childless.

Design

A cross-sectional study.

Setting

A Center of Reproductive Medicine (RMC) at a Swedish University hospital.

Participants

520 women who had undergone at least one IVF cycle at the University Hospital in Linköping between 1986 and 1989. 504 of 520 women (97%) were eligible for follow-up. While 34 women declined, 93 per cent (n=470) of the women agreed to participate. The reference group consisted of 150 women of the Swedish population included in a study that was used to validate the Symptom CheckList (SCL)-90.

Interventions

Follow-up was conducted in 2008–2009. The SCL-90 was used to measure the women's self-perceived mental health and a questionnaire specific for this study was used to retain demographic information.

Outcome measures

The SCL-90 assesses 9 primary dimensions; somatisation, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. There is also a global index of distress.

Results

Women who had previously undergone IVF treatment were at increased risk of symptoms of depression (p=0.017), obsessive-compulsion (p=0.02) and somatisation (p≤0.001) when compared to a reference group. In addition, the women who have remained childless are at increased risk of symptoms of depression (p=0.009) and phobic anxiety (p=0.017).

Conclusions

The majority of the women who have been treated with IVF 20–23 years previously appear to be in good mental health. However, women who remain childless and/or without partner after unsuccessful infertility treatment constitute a vulnerable group even later on in life.
Qualitative complaints and their relation to overall hospital rating using an H-CAHPS-derived instrument
Authors: Kemp Kyle , Warren Sarah , Chan Nancy , McCormack Brandi , Santana Maria , Quan Hude
Published: October 2015

Background and objectives

Due to the multitude of questions in the Hospital-Consumer Assessment of Healthcare Providers and Systems (H-CAHPS) survey, it may be difficult to decide where quality improvement efforts should be focused. Our organisation has supplemented the survey with a ‘patient complaints’ section. The study objectives were to determine (1) the frequency of qualitative complaints and the demographic/clinical profile of patients lodging them, (2) the most frequent complaint themes and their association with overall experience scores and (3) whether overall experience scores varied based upon the complaint action taken by the patient or the degree of patient satisfaction in the handling of complaints.

Methods

From April 2013 to March 2014, 8929 telephone surveys were completed by patients discharged from 93 acute care hospitals in Alberta, Canada. These were successfully linked with the corresponding inpatient record. Open-ended complaints were themed into categories. Mean differences in overall inpatient experience were assessed for each complaint theme, including overall and multiple complaints.

Results

1870 patients (20.9%) reported at least one open-ended complaint. Most frequent complaint themes were nursing (n=491; 5.5% of cohort), medications (n=219; 2.5%) and food (n=193; 2.2%). Increased odds of having a complaint were associated with younger age, being born in Canada and having no documented medical comorbidities. Protective factors were male gender, lower education level, urgent hospital admission, lower resource intensity and length of stay (LOS) <3 days.

Conclusions

This is the first investigation of its type using H-CAHPS-based data in a Canadian context. Through replication of this study, other healthcare organisations may determine the association between open-ended complaints and their own overall experience scores.
Assessing global risk factors for non-fatal injuries from road traffic accidents and falls in adults aged 35–70 years in 17 countries: a cross-sectional analysis of the Prospective Urban Rural Epidemiological (PURE) study
Authors: Raina Parminder , Sohel Nazmul , Oremus Mark , Shannon Harry , Mony Prem , Kumar Rajesh , Li Wei , Wang Yang , Wang Xingyu , Yusoff Khalid , Yusuf Rita , Iqbal Romaina , Szuba Andrzej , Oguz Aytekin , Rosengren Annika , Kruger Annamarie , Chifamba Jephat , Mohammadifard Noushin , Darwish Ebtihal Ahmad , Dagenais Gilles , Diaz Rafael , Avezum Alvaro , Lopez-Jaramillo Patricio , Seron Pamela , Rangarajan Sumathy , Teo Koon , Yusuf Salim
Published: October 2015

Objectives

To assess risk factors associated with non-fatal injuries (NFIs) from road traffic accidents (RTAs) or falls.

Methods

Our study included 151 609 participants from the Prospective Urban Rural Epidemiological study. Participants reported whether they experienced injuries within the past 12 months that limited normal activities. Additional questions elicited data on risk factors. We employed multivariable logistic regression to analyse data.

Results

Overall, 5979 participants (3.9% of 151 609) reported at least one NFI. Total number of NFIs was 6300: 1428 were caused by RTAs (22.7%), 1948 by falls (30.9%) and 2924 by other causes (46.4%). Married/common law status was associated with fewer falls, but not with RTA. Age 65–70 years was associated with fewer RTAs, but more falls; age 55–64 years was associated with more falls. Male versus female was associated with more RTAs and fewer falls. In lower-middle-income countries, rural residence was associated with more RTAs and falls; in low-income countries, rural residence was associated with fewer RTAs. Previous alcohol use was associated with more RTAs and falls; current alcohol use was associated with more falls. Education was not associated with either NFI type.

Conclusions

This study of persons aged 35–70 years found that some risk factors for NFI differ according to whether the injury is related to RTA or falls. Policymakers may use these differences to guide the design of prevention policies for RTA-related or fall-related NFI.