bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Interactive Performance of Zoom-In/Out Gestures Using Electrostatic Tactile Feedback on Touchscreens
Authors: Wang Qinglong , Sun Xiaoying , Cao Dekun , Liu Guohong
Published: March 2020

Tactile feedback added to touchscreens provides users with a high-quality interactive experience. The effect of tactile feedback on typical interaction gestures requires to be evaluated. With a custom-designed electrostatic tactile feedback device, we explore the effects of tactile feedback on zoom-in/out gestures and determine the issues satisfied by the relationship between completion time (CT) and index of difficulty (ID). Specifically, we compare the effect of electrostatic tactile feedback on the efficiency and accuracy of zoom-in/out gestures in three conditions, that is, no tactile feedback, linearly increasing tactile feedback force over operation process, and tactile feedback only in a target area. Then, we study the relationship between CT and ID with tactile feedback added to the target area. Results of experimental data from 12 participants show that tactile feedback added only to a target area can significantly increase operational efficiency and accuracy of zoom-in/out gestures. Furthermore, the relationship between CT and ID agrees well with Fitts’ law, and the correlation coefficient is larger than 0.9.
Regional and oyster microenvironmental scale heterogeneity in the Pacific oyster bacterial community
Authors: King William L , Siboni Nachshon , Kahlke Tim , Dove Michael , O'Connor Wayne , Mahbub Khandaker Rayhan , Jenkins Cheryl , Seymour Justin R , Labbate Maurizio
Published: March 2020

Different organs of a host represent distinct microenvironments resulting in the establishment of multiple discrete bacterial communities within a host. These discrete bacterial communities can also vary according to geographical location. For the Pacific oyster, Crassostrea gigas, the factors governing bacterial diversity and abundance of different oyster microenvironments are poorly understood. In this study, the factors shaping bacterial abundance, diversity and composition associated with the C. gigas mantle, gill, adductor muscle and digestive gland were characterised using 16S (V3-V4) rRNA amplicon sequencing across six discrete estuaries. Both location and tissue-type, with tissue-type being the stronger determinant, were factors driving bacterial community composition. Bacterial communities from wave-dominated estuaries had similar compositions and higher bacterial abundance despite being geographically distant from one another, possibly indicating that functional estuarine morphology characteristics are a factor shaping the oyster bacterial community. Despite the bacterial community heterogeneity, examinations of the core bacterial community identified Spirochaetaceae bacteria as conserved across all sites and samples. Whereas members of the Vulcaniibacterium, Spirochaetaceae and Margulisbacteria, and Polynucleobacter were regionally conserved members of the digestive gland, gill and mantle bacterial communities, respectively. This indicates that baseline bacterial community profiles for specific locations are necessary when investigating bacterial communities in oyster health.
Imaging Alpine crust using ambient noise wave-equation tomography
Authors: Lu Y , Stehly L , Brossier R , Paul A ,   AlpArray Working Group
Published: March 2020

We present an improved crustal Vs model and Moho depth map using ambient noise wave-equation tomography. The so-called ‘ambient noise wave-equation tomography’ is a method to invert seismic ambient noise phase dispersion data based on elastic waveform simulation, which accounts for 3-D and finite-frequency effects. We use cross-correlations of up to 4 yr of continuous vertical-component ambient seismic noise recordings from 304 high-quality broad-band stations in the Alpine region. We use model LSP_Eucrust1.0 obtained from traditional ambient noise tomography as initial model, and we iteratively improve the initial model by minimizing frequency-dependent phase traveltime differences between the observed and synthetic waveforms of Rayleigh waves in the period range 10–50 s. We obtain the final model after 15 iterations with ∼65 per cent total misfit reduction compared to the initial model. At crustal depth, the final model significantly enhances the amplitudes and adjusts the shapes of velocity anomalies. At Moho and upper-mantle depth, the final model corrects an obvious systematic velocity shift of the initial model. The resulting isovelocity Moho map confirms a Moho step along the external side of the external crystalline massifs of the northwestern Alps and reveals underplated gabbroic plutons in the lower most crust of the central and eastern Alps. Ambient noise wave-equation tomography turns out to be a useful tool to refine shear wave velocity models obtained by traditional ambient noise tomography based on ray theory.
Preimplantation loss of fertilized human ova: estimating the unobservable
Authors: Wilcox Allen J , Harmon Quaker , Doody Kevin , Wolf Don P , Adashi Eli Y
Published: March 2020

STUDY QUESTION

What proportion of fertilized human ova are lost before implantation?

SUMMARY ANSWER

An estimated 40 to 50% of fertilized ova fail to implant.

WHAT IS KNOWN ALREADY

Preimplantation loss is not detectable with current technology. Published estimates of preimplantation loss range from 10 to 70%.

STUDY DESIGN, SIZE, DURATION

We combine data from epidemiologic, demographic, laboratory and in vitro fertilization studies to construct an empirical framework for the estimation of preimplantation loss. This framework is summarized in a user-friendly Excel file included in supplement.

PARTICIPANTS/MATERIALS, SETTING, METHODS

We draw from multiple sources to generate plausible estimates of fecundability, sterility, transient anovulation, intercourse patterns and the proportion of ova fertilized in the presence of sperm. We combine these estimates to generate a summary estimate of preimplantation loss. This estimate can be considered an average for couples in their prime reproductive years.

MAIN RESULTS AND THE ROLE OF CHANCE

Under a plausible range of assumptions, we estimate that 40 to 50% of fertilized ova fail to implant.

LIMITATIONS, REASONS FOR CAUTION

A crucial factor in estimating preimplantation loss is the probability that an ovum will be fertilized when exposed to sperm. Human data are available only from in vitro fertilization (IVF), which may not accurately represent events in vivo. We therefore assume a range of in vivo fertilization rates, from 64% (human IVF data) to 90% (mouse data).

WIDER IMPLICATIONS OF THE FINDINGS

Our estimate of preimplantation loss takes into account the biological processes relevant to fertilization and loss. Using this empirical basis for estimation, we find support for the usual assumption that risk of loss is highest in the earliest days following fertilization. Furthermore, this framework can provide improved estimates as better reproductive data become available. To the extent that our estimates are accurate, more fertilized ova are apparently lost in vitro than in vivo, suggesting that further improvements in IVF success rates may be possible.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Professor Adashi serves as Co-Chair of the Safety Advisory Board of Ohana Biosciences, Inc. The other authors have no competing interests.

TRIAL REGISTRATION NUMBER

N/A.
Decoding Decentralized Control Mechanism Underlying Adaptive and Versatile Locomotion of Snakes
Authors: Kano Takeshi , Ishiguro Akio
Published: March 2020

Snakes have no limbs and can move in various environments using a simple elongated limbless body structure obtained through a long-term evolutionary process. Specifically, snakes have various locomotion patterns, which they change in response to conditions encountered. For example, on an unstructured terrain, snakes actively utilize the terrain’s irregularities and move effectively by actively pushing their bodies against the “scaffolds” that they encounter. In a narrow aisle, snakes exhibit concertina locomotion, in which the tail part of the body is pulled forward with the head part anchored, and this is followed by the extension of the head part with the tail part anchored. Furthermore, snakes often exhibit three-dimensional (3-D) locomotion patterns wherein the points of ground contact change in a spatiotemporal manner, such as sidewinding and sinus-lifting locomotion. This ability is achieved possibly by a decentralized control mechanism, which is still mostly unknown. In this study, we address this aspect by employing a synthetic approach to understand locomotion mechanisms by developing mathematical models and robots. We propose a Tegotae-based decentralized control mechanism and use a 2-D snake-like robot to demonstrate that it can exhibit scaffold-based and concertina locomotion. Moreover, we extend the proposed mechanism to 3D and use a 3-D snake-like robot to demonstrate that it can exhibit sidewinding and sinus-lifting locomotion. We believe that our findings will form a basis for developing snake-like robots applicable to search-and-rescue operations as well as understanding the essential decentralized control mechanism underlying animal locomotion.
Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body
Authors: Wang Xuejiao , Li Yingzhuo , Chen Jingyu , Li Zijie , Li Jinhong , Qin Ling
Published: March 2020

Background

Systemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus.

Methods

We implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB).

Results

We found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801.

Conclusion

Our data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.
A Heterodimeric Antibody Fragment for Passive Immunotherapy Against Norovirus Infection
Authors: Yuki Yoshikazu , Kurokawa Shiho , Sato Shintaro , Sasou Ai , Matsumoto Naomi , Suzuki Akio , Sakon Naomi , Goda Yuki , Takeyama Natsumi , Miyoshi Tatsuya , Marcotte Harold , Tanaka Tomoyuki , Hammarstrom Lennart , Kiyono Hiroshi
Published: March 2020

Human noroviruses cause an estimated 685 million infections and 200 000 deaths annually worldwide. Although vaccines against GII.4 and GI.1 genotypes are under development, no information is available regarding vaccines or monoclonal antibodies to other noroviral genotypes. Here, we developed 2 variable-domain llama heavy-chain antibody fragment (VHHs) clones, 7C6 and 1E4, against GII.4 and GII.17 human noroviruses, respectively. Although 7C6 cross-reacted with virus-like particles (VLPs) of GII.17, GII.6, GII.3, and GII.4, it neutralized only GII.4 norovirus. In contrast, 1E4 reacted with and neutralized only GII.17 VLPs. Both VHHs blocked VLP binding to human induced pluripotent stem cell-derived intestinal epithelial cells and carbohydrate attachment factors. Using these 2 VHHs, we produced a heterodimeric VHH fragment that neutralized both GII.4 and GII.17 noroviruses. Because VHH fragments are heat- and acid-stable recombinant monoclonal antibodies, the heterodimer likely will be useful for oral immunotherapy and prophylaxis against GII.4 and GII.17 noroviruses in young, elderly, or immunocompromised persons.
Impact of Sepsis Mandates on Sepsis Care: Unintended Consequences
Authors: Swenson Kai E , Winslow Dean L
Published: March 2020

The creation of dedicated sepsis guidelines and their broad dissemination over the past 2 decades have contributed to significant improvements in sepsis care. These successes have spurred the creation of bundled care mandates by major healthcare payers, such as the Center for Medicare and Medicaid Services. However, despite the likely benefits of guideline-directed sepsis bundles, mandated treatments in sepsis may lead to unintended consequences as the standard of care in sepsis improves. In particular, the heterogeneous spectrum of presentation and disease severity in sepsis, as well as the complexity surrounding the benefits of specific interventions in sepsis, argues for an individualized and titrated approach to interventions: an approach generally not afforded by care mandates. In this review, we review the risks and benefits of mandated care for sepsis, with particular emphasis on the potential adverse consequences of common bundle components such as early empiric antibiotics, weight-based fluid administration, and serum lactate monitoring. Unlike guideline-directed care, mandated care in sepsis precludes providers from tailoring treatments to heterogeneous clinical scenarios and may lead to unintended harms for individual patients.
The Use of Dermal Substitute in Deep Burns of Functional/Mobile Anatomic Areas at Acute Phase After Early Excision and Subsequent Skin Autografting: Dermal Substitute Prevents Functional Limitations
Authors: Gurbuz Kayhan , Demir Mete , Das Koray
Published: March 2020

We aimed to evaluate the results of dermal substitute implantation after early excision in the acute phase of major burn cases within the scope of efforts to reduce contractions and scar formation in functional anatomic areas (face, neck, axilla, elbow, popliteal). Twelve patients with major burn who were treated in the burn center between September 2017 and September 2018 were included in the study. In these patients, Nevelia® dermal substitute was implanted into 24 functional areas with deep partial or full-thickness burns after surgical debridement of the wound. Autologous split-thickness skin graft was applied to these areas after 14 to 21 days. The patients were followed for 4 to 14 months (mean 6 months). Postoperative scar formation was assessed by the Vancouver Scar Scale at the end of the follow-up period. A simple qualitative staging system was used for aesthetic and functional evaluation. The time from burn injury to dermal substitute implantation was 3 to 21 days. Skin graft take was complete in 22 of 24 regions and partial in one of them, while graft loss developed in one region. In the implantation sites, the Vancouver Scar Scale ranged from 1 to 7. The aesthetic and functional evaluation showed excellent/good results in 21 of 24 anatomic regions, moderate results in 2 regions, and poor results in 1 region. The use of dermal substitute in deep burns of functional/mobile anatomic areas at the acute phase after early excision and subsequent skin autografting has opened a new alternative area in the burn surgery arena to prevent contractures and functional limitations.
Evaluation of Chilean Boldo Essential Oil as a Natural Insecticide Against Chrysomya megacephala (Diptera: Calliphoridae)
Authors: Viana Thais de S , Dias Rayane F , Vianna Ana Carolina da S , Moreira Ricardo F A , Aguiar Valéria M
Published: March 2020

Chrysomya megacephala (Fabricius, 1794) is a vector of enteric bacteria, protozoa, helminths, and viruses. These Diptera can also be responsible for secondary myiasis in several animal species. Therefore, it is easy to understand the relevance of studies focusing on C. megacephala dissemination control. The employment of essential oils as natural insecticides must be considered as a promising alternative for the replacement of synthetic insecticides. In this context, the essential oil obtained from Chilean boldo leaves should be highlighted. The aim of the present work was to assess the insecticidal activity of Chilean boldo essential oil against C. megacephala blowflies in different life stages (larva, pupa, and adult). The essential oils were extracted from commercial samples of Chilean boldo leaves by hydrodistillation and were mixed to produce a pool that was employed in the study. Gas chromatographic techniques were used to enable the identification and quantification of the pool’s components. Larvae, pupae, and adult insects of C. megacephala were exposed (topical application) to different concentrations of this essential oil pool. After that, the larvicidal, pupicidal, and insecticidal actions of the oil were tested. Its toxicity might be associated with compounds such as eucalyptol, linalool, α-pinene, limonene, and ascaridole, either acting alone or by synergic effects. Interestingly, the pupae appeared to be stronger than the larvae and adult insects, needing higher doses of essential oil to be killed. The oil’s toxic effects could be useful to control C. megacephala dissemination in all of its development phases.
Soluble CD14 Subtype in Peripheral Blood is a Biomarker for Early Diagnosis of Sepsis
Authors: Zhou Wuqiong , Rao Heping , Ding Qiuming , Lou Xiang , Shen Jianjiang , Ye Bin , Xiang Caixia
Published: March 2020

Objective

To study the value of serum soluble CD14 subtype (sCD14-ST) in early diagnosis of sepsis.

Methods

Seventy-two patients were diagnosed with systemic inflammatory response syndrome, sepsis, or septic shock. Peripheral blood was collected at 0, 12, 24, and 48 hours after admission to the hospital. Levels of sCD14-ST, procalcitonin (PCT), hypersensitive C-reactive protein (CRP), and white blood cells (WBC) were determined.

Results

Levels of sCD14-ST in the patients with septic shock were higher than those in the other patients (P < .01) and peaked at 48 h. PCT and CRP levels were similar in the patients at admission but increased by 5 times to 10 times in the next 48 h, especially in the patients with septic shock. WBC levels remained high and did not change dramatically. Receiver operating characteristic analysis revealed that the area under the curve, sensitivity, and specificity values of sCD14-ST to diagnose sepsis were much higher than those of the other markers.

Conclusion

Compared with PCT, CRP, and WBC, sCD14-ST is a better biomarker for the early diagnosis of sepsis.
The effect of ram-pressure stripping on dwarf galaxies
Authors: Steyrleithner P , Hensler G , Boselli A
Published: March 2020

Ram-pressure stripping (RPS) is a well observed phenomenon of massive spiral galaxies passing through the hot intracluster medium (ICM) of galaxy clusters. For dwarf galaxies (DGs) within a cluster, the transformation from gaseous to gas-poor systems by RPS is not easily observed and must happen in the outskirts of clusters. In a few objects in close by galaxy clusters and the field, RPS has been observed. Since cluster early-type DGs also show a large variety of internal structures (unexpected central gas reservoirs, blue stellar cores, composite radial stellar profiles), we aim in this study to investigate how ram pressure (RP) affects the interstellar gas content and therefore the star formation (SF) activity. Using a series of numerical simulations, we quantify the dependence of the stripped-off gas on the velocity of the infalling DGs and on the ambient ICM density. We demonstrated that SF can be either suppressed or triggered by RP depending on the ICM density and the DGs mass. Under some conditions, RP can compress the gas, so that it is unexpectedly retained in the central DG region and forms stars. When gas clouds are still bound against stripping but lifted from a thin disc and fall back, their new stars form an ellipsoidal (young) stellar population already with a larger velocity dispersion without the necessity of harassment. Most spectacularly, star clusters can form downstream in stripped-off massive gas clouds in the case of strong RP. We compare our results to observations.
Deep spectroscopy in nearby galaxy clusters – V. The Perseus cluster
Authors: Aguerri J A L , Girardi M , Agulli I , Negri A , Dalla Vecchia C , Domínguez Palmero L
Published: March 2020

Dwarfs are the largest population of galaxies in number in the nearby Universe. Deep spectroscopic data are still missing to obtain a better understanding of their formation and evolution processes. This study shows the results obtained from a spectroscopic campaign in the Perseus cluster. We have obtained 963 new galaxy spectra. We have measured the recessional velocity of the galaxies by using a cross-correlation technique. These data have been used to obtain the cluster membership, the dynamics of the galaxies, and the spectroscopic luminosity function (LF) of the cluster. The cluster membership was obtained by using the peak + gap technique, reporting a total of 403 galaxies as cluster members within 1.4r200. The mean velocity and velocity dispersion of the cluster galaxies are Vc = 5258 km s−1 and σc = 1040 km s−1, respectively. We obtained M200 = 1.2 × 1015 M⊙ and r200 = 2.2 Mpc for this cluster. The clusters members were classified blue and red according to their g − r stellar colour. The velocity dispersion of these two families of galaxies is different, indicating that the blue galaxies can be classified as recently accreted into the cluster. We present the spectroscopic galaxy LF of the cluster. This function turned to be flat: α = 0.99 ± 0.06. In addition, blue and red galaxies show similar densities in the faint end of the LF. This indicates that Perseus does not have a population of red dwarf galaxias as large as other nearby clusters. We have compared the LF of the Perseus cluster with other spectroscopic LFs of nearby clusters and those from cosmological simulations. This comparison shows that the spectroscopic LF of nearby galaxy cluster is far from universal.
On the orbital evolution of meteoroid 2020 CD3, a temporarily captured orbiter of the Earth–Moon system
Authors: de la Fuente Marcos C , de la Fuente Marcos R
Published: March 2020

Any near-Earth object (NEO) following an Earth-like orbit may eventually be captured by Earth’s gravity during low-velocity encounters. This theoretical possibility was first attested during the fly-by of 1991 VG in 1991–1992 with the confirmation of a brief capture episode – for about a month in February 1992. Further evidence was obtained when 2006 RH120 was temporarily captured into a geocentric orbit from July 2006 to July 2007. Here, we perform a numerical assessment of the orbital evolution of 2020 CD3, a small NEO found recently that could be the third instance of a meteoroid temporarily captured by Earth’s gravity. We confirm that 2020 CD3 is currently following a geocentric trajectory although it will escape into a heliocentric path by early May 2020. Our calculations indicate that it was captured by the Earth in 2016$_{-4}^{+2}$, median and 16th and 84th percentiles. This episode is longer (4$_{-2}^{+4}$ yr) than that of 2006 RH120. Prior to its capture as a minimoon, 2020 CD3 was probably a NEO of the Aten type, but an Apollo type cannot be excluded; in both cases, the orbit was very Earth-like, with low eccentricity and low inclination, typical of an Arjuna-type meteoroid. A few clone orbits remained geocentric for nearly a century, opening the door to the existence of yet-to-be-detected minimoons that are relatively stable for time-scales comparable to those of unbound quasi-satellites such as (469219) Kamo‘oalewa 2016 HO3. In addition, nearly 10 per cent of the experiments led to brief moon–moon episodes in which the value of the selenocentric energy of 2020 CD3 became negative.
Electronic Consults for Infectious Diseases in a United States Multisite Academic Health System
Authors: Wood Brian R , Bender Jessica A , Jackson Sara , Rosengaus Leah , Pottinger Paul S , Gottlieb Geoffrey S , Dhanireddy Shireesha , Harrington Robert D , Pruzhanskaya Yuliya , Chew Lisa D , Scott John D
Published: March 2020

We launched Infectious Disease electronic consultations (eConsults) in 2018. During the first 15.5 months, primary care practitioners submitted 328 eConsults; the most frequent reasons were a positive culture or polymerase chain reaction (PCR) result, syphilis, and latent tuberculosis. Practitioners commonly requested advice on antimicrobial choice, clinical evaluation, and indications for treatment. Internal phone consultations decreased after eConsult implementation.
High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019
Authors: Cao Wei , Liu Xiaosheng , Bai Tao , Fan Hongwei , Hong Ke , Song Hui , Han Yang , Lin Ling , Ruan Lianguo , Li Taisheng
Published: March 2020

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomized studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.
Building a COVID-19 Vulnerability Index
Authors: DeCapprio Dave , Gartner Joseph , McCall Carol J. , Burgess Thadeus , Kothari Sarthak , Sayed Shaayaan
Published: March 2020

COVID-19 is an acute respiratory disease that has been classified as a pandemic by the World Health Organization. Characterization of this disease is still in its early stages; however, it is known to have high mortality rates, particularly among individuals with preexisting medical conditions. Creating models to identify individuals who are at the greatest risk for severe complications due to COVID-19 will be useful for outreach campaigns to help mitigate the disease’s worst effects. While information specific to COVID-19 is limited, a model using complications due to other upper respiratory infections can be used as a proxy to help identify those individuals who are at the greatest risk. We present the results for three models predicting such complications, with each model increasing predictive effectiveness at the expense of ease of implementation.
Protocol for a mixed methods process evaluation of the Smoking Treatment Optimisation in Pharmacies (STOP) trial
Authors: Jumbe Sandra , Madurasinghe Vichithranie , Houlihan Colin , Jumbe Samantha L , James Wai-Yee , Taylor Stephanie JC , Walton Robert
Published: March 2020

Introduction

Assessing the fidelity of complex behavioural interventions and examining the contextual reasons why such interventions succeed, or fail are important activities but challenging and rarely reported. The Smoking Treatment Optimisation in Pharmacies (STOP) trial is a cluster randomised trial evaluating the effectiveness of a complex intervention to optimise the National Health Service (NHS) Stop Smoking Service delivered in community pharmacies. This complex intervention comprises a training package for pharmacy staff involving motivational interviewing and communication skills aimed at increasing smoking cessation knowledge and proactive client engagement. We report on a process evaluation which was planned alongside the trial to offer findings that will assist in the interpretation of the main trial results and help inform potential implementation in community pharmacy settings on a wider scale.

Methods and analysis

Quantitative data on recruitment and retention process of pharmacies, pharmacy staff and service users has been collected during the trial along with data on dose and fidelity of the intervention delivery from participating intervention arm pharmacies to identify potential implementation issues. Simulated client data on behaviour change skills and display of intervention materials from both control and intervention pharmacies is being assessed. These data will be combined with qualitative data; including adviser-smoker consultation recordings that provide a snapshot of behaviour skills delivery by stop smoking advisers and semi-structured interviews with pharmacy staff and services users from the intervention arm.

Discussion

Published protocols for process evaluations of complex health interventions are still rare despite increasing funding for this work to facilitate understanding of trial outcomes from an implementation perspective. This mixed methods protocol will contribute to the developing literature around the conduct of process evaluation and the value they add to health services research.

Trial registration numberISRCTN16351033.

Strengths and limitations of this study

A planned mixed methods process evaluation that draws together data from different sources to help explain the trial results and establish the feasibility of scaling this complex intervention up in community pharmacy settings.

A strength is the use of a previously tested mystery shopping method to assess fidelity of skills performance at the pharmacy counter

The process evaluation relies on willing pharmacy staff and service users involved in the trial to collect some of the data, which may introduce bias.

This paper also provides a detailed example of how to use the MRC framework for process evaluation of complex interventions to design an extensive process evaluation within trial settings.
More than stoichiometry: the molecular composition of inorganic and organic substrates controls ammonium regeneration by bacteria
Authors: Guo J. , Cherif M.
Published: March 2020

The mineralization of nitrogen (N) and especially the regeneration of ammonium are critical processes performed by bacteria in aquatic ecosystems. Quantifying these processes is complicated because bacteria simultaneously consume and produce ammonium. Here we use experimental data on the effects of the molecular composition of the supplied substrates, combined with a classical stoichiometric model of ammonium regeneration, to demonstrate how the quantification of these processes can be improved. We manipulated a batch culture experiment with an isolated bacterial community by adding three different types of N substrates: dissolved inorganic nitrogen (DIN, nitrate), dissolved organic nitrogen (DON, amino acid) and a mixture of DIN and DON. With such experiment set-up, the ammonium regeneration per se could be easily tracked without using complicated methods (e.g. isotope dilution). We compared the experimental data with the predictions of Goldmanet al’ model (1987) as well as with a revised version, using the measured consumption carbon:nitrogen ratio (C:N ratio), rather than an estimated consumption ratio. We found that, for all substrates, and in particular, mixed substrates where C and N are partially dissociated between different molecules, estimates of ammonium regeneration rates can be improved by measuring the actual consumption C: N ratio.

Importance

Measuring bacterial ammonium regeneration in natural aquatic ecosystem is difficult because bacteria in the field simultaneously consume and produce ammonium. In our experimental design, we used nitrate as the inorganic nitrogen substrate. This way, we could measure separately the uptake and excretion of inorganic nitrogen by bacteria without incorporating cumbersome methods such as isotope dilution. Our experiment allowed us to evaluate the accuracy of various stoichiometric models for the estimation of net bacterial nitrogen regeneration. We found that:

The exact distribution of C and N among the various molecules that make the bulk of DOM is a crucial factor to consider for bacterial net nitrogen regeneration.

For all substrates, and in particular, mixed substrates where C and N are partially dissociated between different molecules, estimates of net nitrogen regeneration rates can be improved by measuring the actual C: N ratio of bacterial consumption.
A comparison of ThinPrep-PreservCyt against four non-volatile transport media for HPV testing at or near the point of care
Authors: Badman S.G. , Vallely A.J. , Pardo C. , Mhango L.P. , Cornall A.M. , Kaldor J.M. , Whiley D.
Published: March 2020

Introduction

The Xpert HPV Test (Cepheid, Sunnyvale, CA) is used at point-of-care for cervical screening in a number of low-and middle-income countries (LMIC). It is validated for use with ThinPrep-PreservCyt (Hologic, Marlborough, MA) transport medium which has a high methanol content and is therefore classified as a dangerous good for shipping; making cost, transportation and use challenging within LMIC. Therefore, we compared the performance of ThinPrep against four non-volatile commercially available media for HPV point-of-care testing.

Methods

Ten-fold serial dilutions were prepared using three HPV cell lines each positive for 16, 18 or 31 and with each suspended in five different media types. The media types consisted of Phosphate Buffered Saline (Thermo Fischer Scientific, Waltham, MA, USA), Sigma Virocult (Medical Wire & Equipment, Wiltshire, England), MSwab (Copan, Brescia BS, Italy) Xpert Transport Media (Cepheid, Sunnyvale, USA) and ThinPrep-PreservCyt (Hologic Inc., Marlborough, MA).

Results

A total of 105 HPV Xpert tests were conducted in a laboratory setting, with 7 ten-fold dilutions of each of the 3 HPV genotypes tested in all 5 media types. The lowest HPV ten-fold dilution detected for any media, or cell line was the fifth dilution. Mswab was the only media to detect HPV to the 5thdilution across all three cell types.

Discussion

Mswab transport media may be a suitable alternative to ThinPrep for Xpert HPV point of care testing and increase HPV detection. A field-based, head to head comparison of both media types using the Xpert HPV assay is warranted to confirm these laboratory-based findings.
Evaluating signals generated in a large-scale sequence symmetry analyses: macrolides and heart failure; and NSAIDs and pneumonia
Authors: Sinnott SJ , Lin KJ , Wang S , Hallas J , Desai R , Schneeweiss S , Gagne JJ
Published: March 2020

Objective

Using US claims data and the most up-to-date pharmacoepidemiological study design tools we aimed to investigate two safety signals for (1) macrolides and heart failure; and (2) non-steroidal anti-inflammatory drugs (NSAIDs) and pneumonia generated from a large-scale screening analysis using a self-controlled sequence symmetry design in Danish data.

Methods

We used IBM Marketscan data to conduct two new-user, active-comparator cohort studies. In the macrolides example, the exposure was clarithromycin or azithromycin and the comparator was amoxicillin/clavulanate, in patients with sinusitis. In the NSAIDs example, the exposure was oral NSAIDs and the comparator was topical diclofenac, in patients with osteoarthritis. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) to adjust for approximately 50 investigator-specified confounders in a propensity score (PS) matched analysis. In a secondary analysis, we used high-dimensional PS (hd-PS) to adjust for 200 additional proxy confounders.

Results

We had 1,012,364 propensity score matched patients exposed to clarithromycin or azithromycin versus amoxicillin/clavulanate. With 162 outcomes among clarithromycin or azithromycin exposed patients and 134 among amoxicillin/clavulanate, the HR for overall heart failure was 1.14 (95% CI 0.90 – 1.43). In the NSAIDs example, we included 94,490 patients after propensity score matching. With 794 pneumonia outcomes among oral NSAID patients and 700 among topical diclofenac, we found HR 0.98 (95% CI 0.89 – 1.09). Some upward bias was suspected as larger HRs were observed in the days immediately following exposure for both the macrolides and NSAIDs examples. We found similar results in the hd-PS matched analyses for both examples.

Conclusion

Our findings for NSAIDs and pneumonia suggest the original signal may have been due to protopathic or detection bias. Our analyses for macrolides and heart failure with short-term follow-up also suggest bias, although we encourage further research.
Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino-acid deletion in nsp2 (Asp268Del)
Authors: Bal Antonin , Destras Grégory , Gaymard Alexandre , Bouscambert-Duchamp Maude , Valette Martine , Escuret Vanessa , Frobert Emilie , Billaud Geneviève , Trouillet-Assant Sophie , Cheynet Valérie , Brengel-Pesce Karen , Morfin Florence , Lina Bruno , Josset Laurence
Published: March 2020

We present the first genetic characterization of a COVID-19 cluster in Europe using metagenomic next-generation sequencing (mNGS). Despite low viral loads, the mNGS workflow used herein allowed to characterize the whole genome sequences of SARS-CoV2 isolated from an asymptomatic patient, in 2 clinical samples collected 1 day apart. Comparison of these sequences suggests viral evolution with development of quasispecies. In addition, the present workflow identified a new deletion in nsp2 (Asp268Del) which was found in all 3 samples originating from this cluster as well as in 37 other viruses collected in England and in Netherlands, suggesting the spread of this deletion in Europe. The impact of Asp268Del on SARS-CoV-2 transmission and pathogenicity, as well as on PCR performances and anti-viral strategy should be rapidly evaluated in further studies.
Genomic Surveillance ofPseudomonas aeruginosain the Philippines from 2013-2014
Authors: Chilam Jeremiah , Argimón Silvia , Limas Marilyn T. , Masim Melissa L. , Gayeta June M. , Lagrada Marietta L. , Olorosa Agnettah M. , Cohen Victoria , Hernandez Lara T. , Jeffrey Benjamin , Abudahab Khalil , Hufano Charmian M. , Sia Sonia B. , Holden Matthew T.G. , Stelling John , Aanensen David M. , Carlos Celia C. ,   on behalf of the Philippines Antimicrobial Resistance Surveillance Program
Published: March 2020

Pseudomonas aeruginosais an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized.

We sequenced the whole genomes of 176P. aeruginosaisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.

Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-β-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population ofP. aeruginosain the Philippines was diverse, with clonal expansions of XDR genomes belonging to multi-locus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, includingblaVIM-2, with differences in gene composition and synteny to otherP. aeruginosaclass 1 integrons described before.

We produced the first comprehensive genomic survey ofP. aeruginosain the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.
Evaluating institutional open access performance: Methodology, challenges and assessment
Authors: Huang Chun-Kai , Neylon Cameron , Hosking Richard , Montgomery Lucy , Wilson Katie , Ozaygen Alkim , Brookes-Kenworthy Chloe
Published: March 2020

Open Access to research outputs is becoming rapidly more important to the global research community and society. Changes are driven by funder mandates, institutional policy, grass-roots advocacy and culture change. It has been challenging to provide a robust, transparent and updateable analysis of progress towards open access that can inform these interventions, particularly at the institutional level. Here we propose a minimum reporting standard and present a large-scale analysis of open access progress across 1,207 institutions world-wide that shows substantial progress being made. The analysis detects responses that coincide with policy and funding interventions. Among the striking results are the high performance of Latin American and African universities, particularly for gold open access, whereas overall open access levels in Europe and North America are driven by repository-mediated access. We present a top-100 of global universities with the world’s leading institutions achieving around 80% open access for 2017 publications.
Genomic Surveillance of Methicillin-ResistantStaphylococcus aureusin the Philippines from 2013-2014
Authors: Masim Melissa L. , Argimón Silvia , Espiritu Holly O. , Magbanua Mariane A. , Lagrada Marietta L. , Olorosa Agnettah M. , Cohen Victoria , Gayeta June M. , Jeffrey Benjamin , Abudahab Khalil , Hufano Charmian M. , Sia Sonia B. , Holden Matthew T.G. , Stelling John , Aanensen David M. , Carlos Celia C. ,   on behalf of the Philippines Antimicrobial Resistance Surveillance Program
Published: March 2020

Methicillin ResistantStaphylococcus aureus(MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about theS. aureuscirculating clones in the Philippines.

We sequenced the whole genomes of 116S. aureusisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type,spatype, SCC-mectype, presence of antimicrobial resistance (AMR) determinants and virulence genes, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.

The MRSA population in the Philippines was composed of a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV, and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South West Pacific clone, but formed a distinct and diverse lineage, with evidence of global dissemination. We showed the independent acquisition of resistance to sulfamethoxazole/trimethoprim across different locations and genetic clones, but mostly in pediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for 8 antibiotics in 7 classes.

We produced the first comprehensive genomic survey ofS. aureusin the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance.
Genomic surveillance ofNeisseria gonorrhoeaein the Philippines, 2013–2014
Authors: Jamoralin Manuel C. , Argimón Silvia , Lagrada Marietta L. , Villamin Alfred S. , Masim Melissa L. , Gayeta June M. , Boehme Karis D. , Olorosa Agnettah M. , Sia Sonia B. , Hufano Charmian M. , Cohen Victoria , Hernandez Lara T. , Jeffrey Benjamin , Abudahab Khalil , Stelling John , Holden Matthew T.G. , Aanensen David M. , Carlos Celia C.
Published: March 2020

Antimicrobial-resistantNeisseria gonorrhoeaeis a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines.

We sequenced the whole genomes of 21N. gonorrhoeaeisolates collected in 2013–2014 by the ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.

Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence ofblaTEMgene, the S91F mutation in thegyrAgene and thetetMgene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, theN. gonorrhoeaemultiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to identification of an international transmission route.

This first genomic survey ofN. gonorrhoeaeisolates collected by ARSP will be used to contextualize prospective surveillance. It highlights the importance of genomic surveillance in the Western Pacific and other endemic regions for understanding the spread of drug-resistant gonorrhoea worldwide.
Evaluating institutional open access performance: Sensitivity analysis
Authors: Huang Chun-Kai , Neylon Cameron , Hosking Richard , Montgomery Lucy , Wilson Katie , Ozaygen Alkim , Brookes-Kenworthy Chloe
Published: March 2020

In the article “Evaluating institutional open access performance: Methodology, challenges and assessment” we develop the first comprehensive and reproducible workflow that integrates multiple bibliographic data sources for evaluating institutional open access (OA) performance. The major data sources include Web of Science, Scopus, Microsoft Academic, and Unpaywall. However, each of these databases continues to update, both actively and retrospectively. This implies the results produced by the proposed process are potentially sensitive to both the choice of data source and the versions of them used. In addition, there remain the issue relating to selection bias in sample size and margin of error. The current work shows that the levels of sensitivity relating to the above issues can be significant at the institutional level. Hence, the transparency and clear documentation of the choices made on data sources (and their versions) and cut-off boundaries are vital for reproducibility and verifiability.