bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccine-enhanced disease: case studies and ethical implications for research and public health
Authors: Jamrozik Euzebiusz , Heriot George , Bull Susan , Parker Michael ,   Oxford-Johns Hopkins Global Infectious Disease Ethics (GLIDE)
Published: June 2021

Vaccination is a cornerstone of global public health. Although licensed vaccines are generally extremely safe, both experimental and licensed vaccines are sometimes associated with rare serious adverse events. Vaccine-enhanced disease (VED) is a type of adverse event in which disease severity is increased when a person who has received the vaccine is later infected with the relevant pathogen. VED can occur during research with experimental vaccines and/or after vaccine licensure, sometimes months or years after a person receives a vaccine. Both research ethics and public health policy should therefore address the potential for disease enhancement. Significant VED has occurred in humans with vaccines for four pathogens: measles virus, respiratory syncytial virus, Staphylococcus aureus, and dengue virus; it has also occurred in veterinary research and in animal studies of human coronavirus vaccines. Some of the immunological mechanisms involved are now well-described, but VED overall remains difficult to predict with certainty, including during public health implementation of novel vaccines. This paper summarises the four known cases in humans and explores key ethical implications. Although rare, VED has important ethical implications because it can cause serious harm, including death, and such harms can undermine vaccine confidence more generally – leading to larger public health problems. The possibility of VED remains an important challenge for current and future vaccine development and deployment. We conclude this paper by summarising approaches to the reduction of risks and uncertainties related to VED, and the promotion of public trust in vaccines.
WOMAN-PharmacoTXA trial: Study protocol for a randomised controlled trial to assess the pharmacokinetics and pharmacodynamics of intramuscular, intravenous and oral administration of tranexamic acid in women giving birth by caesarean section
Authors: Arribas Monica , Roberts Ian , Chaudhri Rizwana , Geer Amber , Prowse Danielle , Lubeya Mwansa Ketty , Kayani Aasia , Javaid Kiran , Grassin-Delyle Stanislas , Shakur-Still Haleema
Published: June 2021

Background: Intravenous tranexamic acid (TXA) within 3 hours of birth significantly reduces death due to bleeding in women with postpartum haemorrhage (PPH). Most PPH deaths occur in the first hours after giving birth and treatment delay decreases survival.  One barrier to rapid TXA treatment is the need for intravenous injection. Intramuscular injection and oral solution of TXA would be easier and faster to administer and would require less training. However, the pharmacokinetics (PK), pharmacodynamics and safety of TXA administered by different routes in pregnant women have not been established. The main aim of this study is to ascertain whether IM and oral solution of TXA will be absorbed at levels sufficient to inhibit fibrinolysis in pregnant women.

Methods: WOMAN-PharmacoTXA is a prospective, randomised, open label trial to be conducted in Zambia and Pakistan.  Adult women undergoing caesarean section with at least one risk factor for PPH will be included.  Women will be randomised to receive one of the following about 1 hour prior to caesarean section: 1-gram TXA IV, 1-gram TXA IM, 4-grams TXA oral solution or no TXA. Randomisation will continue until 120 participants with at least six post randomisation PK samples are included. TXA concentration in maternal blood samples will be measured at baseline and at different time points during 24 hours after receipt of intervention. Blood TXA concentration will be measured from the umbilical cord and neonate.

The primary endpoint is maternal blood TXA concentrations over time. Secondary outcomes include umbilical cord and neonate TXA concentration D-dimer concentration, blood loss and clinical diagnosis of PPH, injection site reactions and maternal and neonate adverse events.

Discussion: The WOMAN-PharmacoTXA trial will provide important data on pharmacokinetics, pharmacodynamics and safety of TXA after IV, intramuscular and oral administration in women giving birth by caesarean section.

Trial registration: ClincalTrials.gov, NCT04274335 (18/02/2020).
The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Questionnaire data capture November 2020 – March 2021
Authors: Smith Daniel , Bowring Claire , Wells Nicholas , Crawford Michael , Timpson Nicholas John , Northstone Kate
Published: June 2021

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study has reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying online questionnaires throughout the pandemic. In November/December 2020, a fourth questionnaire was deployed asking about physical and mental health, lifestyle and behaviours, employment and finances.

G0 participants were offered an online questionnaire between 17th November 2020 and 7th February 2021, while G1 participants were offered both online and paper questionnaires between 1st December 2020 and 19th March 2021. Of 15,844 invitations, 8,643 (55%) participants returned the questionnaire (3,101 original mothers [mean age 58.6 years], 1,172 original fathers/partners [mean age 61.5 years] and 4,370 offspring [mean age 28.4 years]). Of these 8,643 participants, 2,012 (23%) had not returned a previous COVID-19 questionnaire, while 3,575 (41%) had returned all three previous questionnaires.

In this questionnaire, 300 participants (3.5%) reported a previous positive COVID-19 test, 110 (1.3%) had been told by a doctor they likely had COVID-19, and 759 (8.8%) suspected that they had had COVID-19. Based on self-reported symptoms, between October 2020 and February 2021 359 participants (4.2%) were predicted COVID-19 cases.

COVID data is being complemented with linkage to health records and Public Health England pillar testing results as they become available. Data has been released as an update to the previous COVID-19 datasets. It comprises: 1) a standard dataset containing all participant responses to both questionnaires with key sociodemographic factors; and 2) as a composite release coordinating data from the existing resource, thus enabling bespoke research across all areas supported by the study. This data note describes the fourth questionnaire and the data obtained from it.
Portfolio-Wide Optimization of Pharmaceutical R&D Activities Using Mathematical Programming
Authors: Wang Hua , Dieringer Jon , Guntz Steve , Vaidyaraman Shankarraman , Viswanath Shekhar , Lappas Nikolaos H. , Garcia-Munoz Sal , Gounaris Chrysanthos E.
Published: June 2021

The research and development (R&D) management in any major research pharmaceutical company is constantly faced with the need to make complicated activity scheduling and resource allocation decisions, as they carry out scientific work to develop new therapeutic products. This paper describes how we develop a decision support tool that allows practitioners to determine portfolio-wide optimal schedules in a systematic, quantitative, and largely automated fashion. Our tool is based on a novel mixed-integer linear optimization model that extends archetypal multimode resource-constrained project scheduling models in order to accommodate multiple rich features that are pertinent to the Chemistry, Manufacturing, and Controls (CMC) activities carried out within the pharmaceutical R&D setting. The tool addresses this problem at the operational level, determining schedules that are optimal in light of chosen business objectives under activity sequencing, resource availability, and deadline constraints. Applying the tool on current workload data demonstrates its tractability for practical adoption. We further illustrate how, by utilizing the tool under different input instances, one may conduct various tactical analyses to assess the system’s ability to cope with sudden changes or react to shifting management priorities.
Limousine Service Management: Capacity Planning with Predictive Analytics and Optimization
Authors: Liu Peng , Chen Ying , Teo Chung-Piaw
Published: June 2021

Thelimousine service in luxury hotels is an integral component of the whole customer journey in the hospitality industry. One of the largest hotels in Singapore manages a fleet of both in-house and outsourced vehicles around the clock, serving 9,000 trips per month on average. The need for vehicles may scale up rapidly, especially during special events and festive periods in the country. The excess demand is met by having additional outsourced vehicles on standby, incurring millions of dollars of additional expenses per year for the hotel. Determining the required number of limousines by hour of the day is a challenging service capacity planning problem. In this paper, a recent transformational journey to manage this problem for the hotel is introduced, having driven up to S$3.2 million of savings per year while improving the service level. The approach builds on widely available open-source statistical and spreadsheet optimization tools, along with robotic process automation, to optimize the schedule of the hotel’s fleet of limousines and drivers and to support decision making for planners and controllers to cultivate sustained business value.
Seasonal deformation monitoring of the northern Yellow River Delta based on InSAR technology
Authors: Jing Shaodong , Zhong Chuhan , Wang Qiang , Wang Xiaying , Zhang Shuangcheng , Niu Yufen
Published: June 2021

Due to overexploitation of natural resources in the northern Yellow River Delta and the resulting land subsidence, interferometric synthetic aperture radar (InSAR) technology is utilized to analyze the deformation trend. Based on Advanced Land Observation Satellite PHASE Array Type L-band Synthetic Aperture Radar and Sentinel-1 data, this paper obtains the annual subsidence rate in two time periods (2007–2010 and 2017–2020) and verifies the correctness by comparing the ascending and descending orbit results. Subsequently, the 11 deformation interference pairs of the three-month interval are extracted to analyze the time series displacement of deformation areas. The results show that there are three large-scale subsidence areas with maximum annual subsidence of 250 mm, all of which are located in the oil or brine exploitation areas, and each deformation area displays a larger linear rate from January to May and then displays different nonlinear deformation from June to December.
Adjustable multichannel terahertz resonator
Authors: Li Da , Li Jiu-sheng
Published: June 2021

Most reported terahertz devices are relatively simple to control by means of external
applied electricity, light, heat, magnetism, etc. In the practical
application of a terahertz system, the devices with a variety of
adjustable methods are promising. In this paper, we design a
rectangular-ambulatory-plane metal groove structure on apolymer
polydimethylsiloxane (PDMS) substrate with graphene embedded in the
metal grooves. The resonance performance of the proposed structure can
be controlled by changing the external force and graphene chemical
potential. Three electromagnetic-induced reflection peaks of the
structure are achieved at 0.54, 0.60, and 0.63 THz with reflectivity
of 89.6%, 77.1%, and 75.7%, respectively. Under the change of the
applied bias voltage and external force, the reflectivity of the three
reflection peaks of the resonator can be regulated freely. In
addition, the proposed structure is polarization-insensitive and
maintains stable terahertz reflection peaks with incident angles up to
25°.
Suppressing stimulated Raman scattering by adopting a composite cavity in a narrow linewidth fiber oscillator
Authors: Zhang Song , Zhang Wanru , Jiang Man , Liu Wei , Ma Pengfei , Li Can , Su Rongtao , Zhou Pu , Jiang Zongfu
Published: June 2021

The master oscillator power amplifier structure has been widely employed to realize high-power and narrow-linewidth output in fiber lasers. However, the stimulated Raman scattering (SRS) effect would appear in high-power operation and even become an important limitation on further power scaling, especially when the seed lasers are based on a fiber Bragg grating (FBG) pair. In order to improve SRS suppressing ability, a composite cavity structure was demonstrated by employing an additional wide-bandwidth low-reflectivity FBG outside the conventional oscillator. After passing through a piece of 50 m SMF-28e fiber, thanks to the improved temporal stability of the composite oscillator, the proportion of Raman Stokes light dropped dramatically compared with the proportion in a conventional fiber oscillator. This composite cavity design could provide a simple and compact approach for SRS suppression in a high-power narrow-linewidth fiber laser system.
Unified analytical method for Zernike coefficient transformation of scaled, rotated, and translated pupils based on Shack’s vector multiplication
Authors: Zhang Yongfeng , Wang Shengqian , Xian Hao , Rao Changhui
Published: June 2021

Zernike polynomials play an essential role in characterizing and analyzing wavefront aberrations. Transformation of weighted coefficients for Zernike modes is required when pupil scaling, rotation, and/or translation exist. Here, a novel method based on Shack’s vector multiplication is first proposed to derive the transformation relation. The derived modes resulting from pupil scaling, rotation, and/or translation for each individual mode are easily indicated via this method; thus, the effect of each kind of pupil change could be studied qualitatively and quantitatively. Its remarkable computational efficiency against the direct integral is demonstrated by simulation. The method introduced here provides a generalized methodology to analyze the relationship between weighted coefficients for different description basis sets.
On-sky results for the integrated microlens ring tip-tilt sensor
Authors: Hottinger Philipp , Harris Robert J. , Crass Jonathan , Dietrich Philipp-Immanuel , Blaicher Matthias , Bechter Andrew , Sands Brian , Morris Timothy , Basden Alastair G. , Bharmal Nazim Ali , Heidt Jochen , Anagnos Theodoros , Neureuther Philip L. , Glück Martin , Power Jennifer , Pott Jörg-Uwe , Koos Christian , Sawodny Oliver , Quirrenbach Andreas
Published: June 2021

We present the first on-sky results of the microlens ring tip-tilt sensor. This sensor uses a 3D printed microlens ring feeding six multimode fibers to sense misaligned light, allowing centroid reconstruction. A tip-tilt mirror allows the beam to be corrected, increasing the amount of light coupled into a centrally positioned single-mode (science) fiber. The sensor was tested with the iLocater acquisition camera at the Large Binocular Telescope in Tucson, Arizona, in November 2019. The limit on the maximum achieved rms reconstruction accuracy was found to be

0.19
λ

/

D

in both tip and tilt, of which approximately 50% of the power originates at frequencies below 10 Hz. We show the reconstruction accuracy is highly dependent on the estimated Strehl ratio and simulations support the assumption that residual adaptive optics aberrations are the main limit to the reconstruction accuracy. We conclude that this sensor is ideally suited to remove post-adaptive optics noncommon path tip-tilt residuals. We discuss the next steps for concept development, including optimization of the lens and the fiber, tuning of the correction algorithm, and selection of optimal science cases.
Large-area TaN superconducting microwire single photon detectors for X-ray detection
Authors: Yang Can , Si Mengting , Zhang Xingyu , Yu Aobo , Huang Jia , Pan Yiming , Li Hao , Li Lingyun , Wang Zhen , Zhang Shuo , Xia Jingkai , Liu Zhi , Guo Han , You Lixing
Published: June 2021

With the development of superconducting nanowire single photon detectors, increasing numbers of important applications are being explored, covering not only low-energy optical photon detection but also high-energy photon and particle detection. In this work, 100-nm-thick TaN superconducting microwire single photon detectors (SMSPDs) with large active areas were prepared for X-ray detection, and their response characteristics to X-rays were studied. The results showed that our TaN SMSPDs were able to detect X-rays at a wide range of bias currents and working temperatures. The detectors could distinguish different energy X-rays under suitable working conditions, and the energy resolving power was strongly related to the bias current.
Generation and compression of 10-fs deep ultraviolet pulses at high repetition rate using standard optics
Authors: Bruder Lukas , Wittenbecher Lukas , Kolesnichenko Pavel V. , Zigmantas Donatas
Published: June 2021

The generation and characterization of ultrashort laser pulses in the deep ultraviolet spectral region is challenging, especially at high pulse repetition rates and low pulse energies. Here, we combine achromatic second harmonic generation and adaptive pulse compression for the efficient generation of sub-10 fs deep ultraviolet laser pulses at a laser repetition rate of 200 kHz. Furthermore, we simplify the pulse compression scheme and reach pulse durations of ≈10 fs without the use of adaptive optics. We demonstrate straight-forward tuning from 250 to 320 nm, broad pulse spectra of up to 63 nm width, excellent stability and a high robustness against misalignment. These features make the approach appealing for numerous spectroscopy and imaging applications.
Superconducting nanowire single-photon detector with 3D-printed free-form microlenses
Authors: Xu Yilin , Kuzmin Artem , Knehr Emanuel , Blaicher Matthias , Ilin Konstantin , Dietrich Philipp-Immanuel , Freude Wolfgang , Siegel Michael , Koos Christian
Published: June 2021

We present an approach to increase the effective light-receiving area of superconducting nanowire single-photon detectors (SNSPD) by free-form microlenses. These lenses are printed in situ on top of the sensitive detector areas using high-resolution multi-photon lithography. We demonstrate a detector based on niobium-nitride (NbN) nanowires with a 4.5 µm × 4.5 µm sensitive area, supplemented with a lens of 60-µm-diameter. For a plane-wave-like free-space illumination at a wavelength of 1550 nm, the lensed sensor has a 100-fold increased effective collection area, which leads to a strongly enhanced system detection efficiency without the need for long nanowires. Our approach can be readily applied to a wide range of sensor types. It effectively overcomes the inherent design conflict between high count rate, high timing accuracy, and high fabrication yield on the one hand and high collection efficiency through a large effective detection area on the other hand.
Trapped light scattering within optical coatings: a multilayer roughness-coupling process
Authors: Amra Claude , Zerrad Myriam , Lequime Michel
Published: June 2021

Despite numerous works devoted to light scattering in multilayer optics, trapped scattering has not been considered until now. This consists in a roughness-coupling process at each interface of the multilayer, giving rise to electromagnetic modes traveling within the stack. Such a modal scattering component is today necessary for completing the energy balance within high-precision optics including mirrors for gyro-lasers and detection of gravitational waves, where every ppm (part per million) must be accounted for. We show how to calculate this trapped light and compare its order of magnitude with the free space scattering component emerging outside the multilayer.
Broadband (8.5–13.5  µm) intra-pulse difference frequency generation in a LiGaS2 crystal of a 90  fs 744  nm laser pulse after its continuous redshift in air
Authors: Grudtsyn Ya. V. , Kinyaevskiy I. O. , Koribut A. V. , Seleznev L. V. , Gerasimova Yu. A. , Rogashevskii A. A. , Ionin A. A.
Published: June 2021

Broadband frequency downconversion of a 90 fs 744 nm Ti:sapphire laser pulse into the mid-infrared (IR) was demonstrated via its filamentation-induced self-frequency shift in air and subsequent intra-pulse difference frequency generation in a

L
i
G
a
S

2

crystal. The filamentation of the laser pulse in air provided its continuous spectral broadening to the Stokes wing with spectral humps separated by

∼

1000

c
m

−
1

that was appropriate for the laser pulse difference frequency conversion into the mid-IR. The difference frequency emission spectrum spanned from 8.5 to 13.5 µm at the

e

−
2

level. The transform limited pulse duration of the mid-IR pulse was 47 fs, which corresponded to a 1.3-cycle laser pulse. Energy conversion efficiency was up to

10

−
4

and

5
⋅
10

−
4

without and with chirp compensation, respectively.
Hot–electron emission enhancement by deep UV surface plasmon resonance on an aluminum periodic disk–hole array
Authors: Morisawa Hirofumi , Ono Atsushi , Inami Wataru , Kawata Yoshimasa
Published: June 2021

We present the enhancement of the hot-electron emissions by the enhanced electric field with deep UV surface plasmon resonance (DUV-SPR). An aluminum disk–hole array was designed using the finite-difference time-domain (FDTD) method for enhancing the electric field by the disk–hole cavity coupling. We found that the photoelectron emission efficiencies were experimentally improved by four times and that the disk–hole distance was a key factor to induce the strong disk–hole coupling. The aluminum disk–hole array with DUV-SPR would be expected for many applications, such as the highly sensitive photodetectors, the photoelectron guns, and the efficient photocatalysts.
Generating X-rays with orbital angular momentum in a free-electron laser oscillator
Authors: Huang Nanshun , Deng Haixiao
Published: June 2021

Light with orbital angular momentum (OAM) provides new insights into a wide range of physical phenomena and has engendered advanced applications in various fields. Additionally, interest in X-ray OAM has been rapidly rising. We present a straightforward method to generate intense OAM beams from an X-ray free-electron laser oscillator (XFELO). The method leverages Bragg mirrors and longitudinal-transverse mode coupling to enable mode selection in a conventional XFELO configuration, thereby natively producing the fully coherent hard X-ray beams carrying OAM. Furthermore, simulation results demonstrate that fully coherent hard X-ray OAM beams at 1 MHz with a pulse energy of about 120 µJ can be generated without the optical mode converters. This simple approach could significantly advance the creation of X-ray OAM while stimulating the development of experimental methods.
Three-dimensional topology optimization model to simulate the external shapes of bone
Authors: Sakashita Misaki , Yamasaki Shintaro , Yaji Kentaro , Kawamoto Atsushi , Kondo Shigeru
Published: June 2021

Elucidation of the mechanism by which the shape of bones is formed is essential for understanding vertebrate development. Bones support the body of vertebrates by withstanding external loads, such as those imposed by gravity and muscle tension. Many studies have reported that bone formation varies in response to external loads. An increased external load induces bone synthesis, whereas a decreased external load induces bone resorption. This relationship led to the hypothesis that bone shape adapts to external load. In fact, by simulating this relationship through topology optimization, the internal trabecular structure of bones can be successfully reproduced, thereby facilitating the study of bone diseases. In contrast, there have been few attempts to simulate the external structure of bones, which determines vertebrate morphology. However, the external shape of bones may be reproduced through topology optimization because cells of the same type form both the internal and external structures of bones. Here, we constructed a three-dimensional topology optimization model to attempt the reproduction of the external shape of teleost vertebrae. In teleosts, the internal structure of the vertebral bodies is invariable, exhibiting an hourglass shape, whereas the lateral structure supporting the internal structure differs among species. Based on the anatomical observations, we applied different external loads to the hourglass-shaped part. The simulations produced a variety of three-dimensional structures, some of which exhibited several structural features similar to those of actual teleost vertebrae. In addition, by adjusting the geometric parameters, such as the width of the hourglass shape, we reproduced the variation in the teleost vertebrae shapes. These results suggest that a simulation using topology optimization can successfully reproduce the external shapes of teleost vertebrae. By applying our topology optimization model to various bones of vertebrates, we can understand how the external shape of bones adapts to external loads.
A network modelling approach to assess non-pharmaceutical disease controls in a worker population: An application to SARS-CoV-2
Authors: Hill Edward M. , Atkins Benjamin D. , Keeling Matt J. , Dyson Louise , Tildesley Michael J.
Published: June 2021

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create ‘COVID-secure’ workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread.
Methodology for rigorous modeling of protein conformational changes by Rosetta using DEER distance restraints
Authors: del Alamo Diego , Jagessar Kevin L. , Meiler Jens , Mchaourab Hassane S.
Published: June 2021

We describe an approach for integrating distance restraints from Double Electron-Electron Resonance (DEER) spectroscopy into Rosetta with the purpose of modeling alternative protein conformations from an initial experimental structure. Fundamental to this approach is a multilateration algorithm that harnesses sets of interconnected spin label pairs to identify optimal rotamer ensembles at each residue that fit the DEER decay in the time domain. Benchmarked relative to data analysis packages, the algorithm yields comparable distance distributions with the advantage that fitting the DEER decay and rotamer ensemble optimization are coupled. We demonstrate this approach by modeling the protonation-dependent transition of the multidrug transporter PfMATE to an inward facing conformation with a deviation to the experimental structure of less than 2Å Cα RMSD. By decreasing spin label rotamer entropy, this approach engenders more accurate Rosetta models that are also more closely clustered, thus setting the stage for more robust modeling of protein conformational changes.
A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease
Authors: Ness Natalie , Schultz Simon R.
Published: June 2021

Alzheimer’s Disease (AD) is characterized by progressive neurodegeneration and cognitive impairment. Synaptic dysfunction is an established early symptom, which correlates strongly with cognitive decline, and is hypothesised to mediate the diverse neuronal network abnormalities observed in AD. However, how synaptic dysfunction contributes to network pathology and cognitive impairment in AD remains elusive. Here, we present a grid-cell-to-place-cell transformation model of long-term CA1 place cell dynamics to interrogate the effect of synaptic loss on network function and environmental representation. Synapse loss modelled after experimental observations in the APP/PS1 mouse model was found to induce firing rate alterations and place cell abnormalities that have previously been observed in AD mouse models, including enlarged place fields and lower across-session stability of place fields. Our results support the hypothesis that synaptic dysfunction underlies cognitive deficits, and demonstrate how impaired environmental representation may arise in the early stages of AD. We further propose that dysfunction of excitatory and inhibitory inputs to CA1 pyramidal cells may cause distinct impairments in place cell function, namely reduced stability and place map resolution.
Orthobunyaviruses in the Caribbean: Melao and Oropouche virus infections in school children in Haiti in 2014
Authors: Elbadry Maha A. , Durães-Carvalho Ricardo , Blohm Gabriela M. , Stephenson Caroline J. , Loeb Julia C. , White Sarah K. , Telisma Taina , Chavannes Sonese , Beau De Rochars Valery M. , Salemi Marco , Morris J. Glenn , Lednicky John A.
Published: June 2021

We report the identification of two orthobunyaviruses, Melao virus (MELV) and Oropouche virus (OROV), in plasma specimens from Haitian children with acute febrile illness who presented during outbreaks caused by alpha- and flaviviruses in 2014. Heretofore not described as a human pathogen, MELV was isolated in cell culture from the plasma of five case patients. OROV RNA was detected in the plasma of an additional child, using an unbiased sequencing approach, with phylogenetic inference suggesting a close relationship with strains from Brazil. Abdominal pain was reported by four case patients with MELV infections, with lymphadenopathy noted in two cases. Our findings document the occurrence of these orthobunyaviruses within the Caribbean region and highlight the critical importance of surveillance with viral genome sequence analyses to identify outbreaks caused by these and other emerging viruses.
Use of auxiliary devices during retreatment of direct resin composite veneers
Authors: Guarnieri Fabrício Daniel Finotti , Briso André Luiz Fraga , Ramos Fernanda de Souza e Silva , Esteves Lara Maria Bueno , Omoto Érika Mayumi , Sundfeld Renato Herman , Fagundes Ticiane Cestari
Published: June 2021

The removal of direct composite veneers, when the retreatment is necessary, represents a challenge to the clinician, since the healthy dental structure must be preserved. Thus, the aim of this study was to compare the accuracy provided by different auxiliary devices during retreatment of direct composite veneers. Seventy-five bovine teeth were prepared for direct composite veneers, scanned (T1), and restored. Specimens were divided into 5 groups for retreatment: conventional high-speed handpiece without auxiliary device (WD); high-speed handpiece with a white LED (WL); high-speed handpiece with an UV light (UL); electric motor and multiplier 1/5 handpiece (EM); and conventional high-speed handpiece using magnifying loupe (ML). After retreatments, other scanning was performed (T2). Changes on dental wear or composite residues areas, as well as, the average between wear and presence of residues were measured. Data were submitted to Kruskal-Wallis and Dunn’s post-test (p≤ 0.05). There were greater areas of wear for ML, being statistically superior to WD and EM groups. The ML presented smaller residues areas, being statistically lower than the WD and EM groups. Regarding the average between wear and the presence of resin residues, additional wear occurred after re-preparation, regardless of the group. Magnifying loupe promoted greater areas of wear and smaller areas of resin residues than conventional high-speed handpiece and electric motor. Both techniques using light accessories did not differ from other ones.
Shifting networks and mixing metals: Changing metal trade routes to Scandinavia correlate with Neolithic and Bronze Age transformations
Authors: Nørgaard Heide W. , Pernicka Ernst , Vandkilde Helle
Published: June 2021

Based on 550 metal analyses, this study sheds decisive light on how the Nordic Bronze Age was founded on metal imports from shifting ore sources associated with altered trade routes. On-and-off presence of copper characterised the Neolithic. At 2100–2000 BC, a continuous rise in the flow of metals to southern Scandinavia begins. First to arrive via the central German Únětician hubs was high-impurity metal from the Austrian Inn Valley and Slovakia; this was complemented by high-tin British metal, enabling early local production of tin bronzes. Increased metal use locally fuelled the leadership competitions visible in the metal-led material culture. The Únětice downfall c.1600 BC resulted for a short period in a raw materials shortage, visible in the reuse of existing stocks, but stimulated direct Nordic access to the Carpathian basin. This new access expedited innovations in metalwork with reliance on chalcopyrite from Slovakia, as well as opening new sources in the eastern Alps, along an eastern route that also conveyed Baltic amber as far as the Aegean. British metal plays a central role during this period. Finally, from c.1500 BC, when British copper imports ceased, the predominance of novel northern Italian copper coincides with the full establishment of the NBA and highlights a western route, connecting the NBA with the southern German Tumulus culture and the first transalpine amber traffic.
Antidiabetic activities of Bolanthus spergulifolius (Caryophyllaceae) extracts on insulin-resistant 3T3-L1 adipocytes
Authors: Derici Gizem Ece , Özdaş Sibel , Canatar İpek , Koç Murat
Published: June 2021

Diabetes mellitus (DM) is a metabolic disorder with chronic hyperglycemia featured by metabolic outcomes owing to insufficient insulin secretion and/or insulin effect defect. It is critical to investigate new therapeutic approaches for T2DM and alternative, natural agents that target molecules in potential signal pathways. Medicinal plants are significant resources in the research of alternative new drug active ingredients.Bolanthus spergulifolius (B.spergulifolius)is one of the genera of the family Caryophyllaceae. In this study, it was explored the potential anti-diabetic effectsin vitroofB.spergulifoliusextracts on 3T3-L1 adipocytes. The total phenolic contents (TPC) of methanolic (MeOH), ethyl acettate (EA) and aqueous extracts ofB.spergulifoliuswere evaluated via Folin-Ciocateau.B.spergulifoliusextracts showing highly TPC (Aqueous< MeOH< EA) and their different concentrations were carried out on preadipocytes differentiated in to mature 3T3-L1 adipocytes to investigate their half-maximal (50%) inhibitory concentration (IC50) value by using Thiazolyl blue tetrazolium bromide (MTT) assay. The IC50of MeOH, EA and Aqueous extracts were observed as 305.7 ± 5.583 μg/mL, 567.4 ± 3.008 μg/mL, and 418.3 ± 4.390 μg/mL and used for further experiments. A live/dead assay further confirmed the cytotoxic effects of MeOH, EA and Aqueous extracts (respectively, 69.75 ± 1.70%, 61.75 ± 1.70%, 70 ± 4.24%, and for all p< 0.05). Also, effects of extracts on lipid accumulation in mature 3T3-L1 adipocytes were evaluated by Oil-Red O staining assay. The extracts effectively decreased lipid-accumulation compared to untreated adipocytes (for all p< 0.05). Moreover, effect of extracts on apoptosis regulated by theBaxandBcl-2was investigated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The extracts significantly induced apoptosis by up-regulating pro-apoptoticBaxexpression but down-regulated anti-apoptoticBcl-2gene expression compared to untreated adipocytes (for all p< 0.05). TheGlut-4expression linked with insulin resistance was determined by qRT-PCR, Western-blot analysis, and immunofluorescence staining. In parallel, the expression of Glut-4 in adipocytes treated with extracts was significantly higher compared to untreated adipocytes (for all p< 0.05). Extracts significantly suppressed cell migration after 30 h of wounding in a scratch-assay (for all p< 0.05). Cell morphology and diameter were further evaluated by phase-contrast microscopy, scanning electron microscopy, Immunofluorescence with F-Actin and Giemsa staining. The adipocytes treated with extracts partially lost spherical morphology and showed smaller cell-diameter compared to untreated adipocytes (for all p< 0.05). In conclusion, these results suggest that extracts ofB.spergulifoliuscause to an induce apoptosis, decrease lipid-accumulation, wound healing, up-regulating Glut-4 level and might contribute to reducing of insulin-resistance in DM.
Exploring daily time-use patterns: ATUS-X data extractor and online diary visualization tool
Authors: Kolpashnikova Kamila , Flood Sarah , Sullivan Oriel , Sayer Liana , Hertog Ekaterina , Zhou Muzhi , Kan Man-Yee , Suh Jooyeoun , Gershuny Jonathan
Published: June 2021

Time-use data can often be perceived as inaccessible by non-specialists due to their unique format. This article introduces the ATUS-X diary visualization tool that aims to address the accessibility issue and expand the user base of time-use data by providing users with opportunity to quickly visualize their own subsamples of the American Time Use Survey Data Extractor (ATUS-X). Complementing the ATUS-X, the online tool provides an easy point-and-click interface, making data exploration readily accessible in a visual form. The tool can benefit a wider academic audience, policy-makers, non-academic researchers, and journalists by removing accessibility barriers to time use diaries.
Reported health and social consequences of the COVID-19 pandemic on vulnerable populations and implemented solutions in six West African countries: A media content analysis
Authors: Saalim Khalida , Sakyi Kwame S. , Fatema-Tuz-Zohra  , Morrison Emily , Owusu Prince , Dalglish Sarah L. , Kanyangarara Mufaro
Published: June 2021

Coronavirus has spread worldwide with over 140 million cases and resulting in more than 3 million deaths between November 2019 to April 2021, threatening the socio-economic and psychosocial stability of many families and communities. There has been limited research to understand the consequences of COVID-19 on vulnerable populations in West Africa, and whether such consequences differ by countries’ previous experience with Ebola. Using a media analysis of leading online news sources, this study identified the populations particularly vulnerable to the threats of the COVID-19 pandemic, described the consequences of COVID-19 experienced by these populations, and reported on the solutions to address them. All articles from the selected news sources published between January 1 and June 30, 2020 on 6 West African countries were imported into Dedoose. A total of 4,388 news articles were coded for excerpts on vulnerable populations, only 285 excerpts of which mentioned the existing effects of COVID-19 on vulnerable populations or implemented solutions. News articles from countries with past experience with Ebola were more likely to mention the pandemic’s effects on vulnerable populations, especially on incarcerated people. Vulnerable groups were reported to have experienced a range of effects including economic disruptions, heightened domestic and sexual abuse, arbitrary arrests, health care inaccessibility, and educational challenges throughout the pandemic. With implications for the achievement of the Sustainable Development Goals (SDG) for 2030 in West Africa, these countries should consider and focus more strategic efforts on vulnerable populations to overcome their fight against the COVID-19 pandemic and to achieve the SDG for 2030.
Extracellular proteolytic activation of Pseudomonas aeruginosa aminopeptidase (PaAP) and insight into the role of its non-catalytic N-terminal domain
Authors: Axelrad Itschak , Safrin Mary , Cahan Rivka , Suh Sang-Jin , Ohman Dennis E. , Kessler Efrat
Published: June 2021

Pseudomonas aeruginosa secretes several endopeptidases, including elastase, alkaline proteinase (Apr), a lysine-specific endopeptidase (LysC), and an aminopeptidase (PaAP), all of which are important virulence factors. Activation of the endopeptidases requires removal of an inhibitory N-terminal propeptide. Activation of pro-PaAP, in contrast, requires C-terminal processing. The activating proteases of pro-PaAP and their cleavage site(s) have not yet been defined. Studying pro-PaAP processing in a wild type P. aeruginosa strain and strains lacking either elastase or both elastase and Apr, we detected three processing variants, each ~56 kDa in size (AP56). Activity assays and N- and C-terminal sequence analyses of these variants pointed at LysC as the principal activating protease, cleaving a Lys512-Ala513 peptide bond at the C-terminal end of pro-PaAP. Elastase and/or Apr are required for activation of LysC, suggesting both are indirectly involved in activation of PaAP. To shed light on the function(s) of the N-terminal domain of AP56, we purified recombinant AP56 and generated from it the 28 kDa catalytic domain (AP28). The kinetic constants (Km and Kcat) for hydrolysis of Leu-, Lys-, Arg- and Met-p-nitroanilide (pNA) derivatives by AP56 and AP28 were then determined. The catalytic coefficients (Kcat/Km) for hydrolysis of all four substrates by AP28 and AP56 were comparable, indicating that the non-catalytic domain is not involved in hydrolysis of small substrates. It may, however, regulate hydrolysis of natural peptides/proteins. Lys-pNA was hydrolyzed 2 to 3-fold more rapidly than Leu-pNA and ~8-fold faster than Arg- or Met-pNA, indicating that Lys-pNA was the preferred substrate.
New relevance and significance measures to replace p-values
Authors: Stahel Werner A.
Published: June 2021

The p-value has been debated exorbitantly in the last decades, experiencing fierce critique, but also finding some advocates. The fundamental issue with its misleading interpretation stems from its common use for testing the unrealistic null hypothesis of an effect that is precisely zero. A meaningful question asks instead whether the effect is relevant. It is then unavoidable that a threshold for relevance is chosen. Considerations that can lead to agreeable conventions for this choice are presented for several commonly used statistical situations. Based on the threshold, a simple quantitative measure of relevance emerges naturally. Statistical inference for the effect should be based on the confidence interval for the relevance measure. A classification of results that goes beyond a simple distinction like “significant / non-significant” is proposed. On the other hand, if desired, a single number called the “secured relevance” may summarize the result, like the p-value does it, but with a scientifically meaningful interpretation.
Optical characterization of 3D printed PLA and ABS filaments for diffuse optics applications
Authors: Amendola Caterina , Lacerenza Michele , Pirovano Ileana , Contini Davide , Spinelli Lorenzo , Cubeddu Rinaldo , Torricelli Alessandro , Re Rebecca
Published: June 2021

The interest for Fused Deposition Modelling (FDM) in the field of Diffuse Optics (DO) is rapidly increasing. The most widespread FDM materials are polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS), thanks to their low cost and easiness-to-print. This is why, in this study, 3D printed samples of PLA and ABS materials were optically characterized in the range from the UV up to the IR wavelengths, in order to test their possible employment for probe construction in DO applications. To this purpose, measurements with Near Infrared Spectroscopy and Diffuse Correlation Spectroscopy techniques were considered. The results obtained show how the material employed for probe construction can negatively affect the quality of DO measurements.
Neonatal thyrotropin levels and auditory neural maturation in full-term newborns
Authors: Pallone Leticia Valerio , Navarra Laura Carvalho , Gonçalves Gleice Aline , de Jesus Felipe Alves , Melo Debora Gusmão , Ferreira Rodrigo Alves , Germano Carla Maria Ramos
Published: June 2021

Objective

This study aimed to look for a possible relationship between thyrotropin (TSH) values from neonatal bloodspot screening testing and newborn lower auditory pathway myelinization evaluated using the brainstem evoked response audiometry (ABR) test.

Methods

Sixty-two healthy full-term newborns without perinatal problems were enrolled in the study. TSH results were collected from neonatal bloodspot screening data and were below the test cut-off level (15μUI/mL). The TSH test was performed between three and seven days, and the ABR test was performed in the first 28 days of life. The newborns were divided into two groups: Group 1 (n = 35), TSH between 0 and 5μUI/mL, and group 2 (n = 27), TSH between 5 and 15μUI/mL. Data are presented as mean ± SD, median, or percentage, depending on the variable.

Results

Wave latency and interpeak interval values for Groups 1 and 2 were as follows: Wave I: 1.8 ± 0.1 and 1.7 ± 0.1; Wave III: 4.4 ± 0.1 and 4.4 ± 0.1; Wave V: 6.9 ± 0.1 and 6.9 ± 0.1; interval I–III: 2.6 ± 0.1 and 2.6 ± 0.1; interval I–V: 5.1 ± 0.1 and 5.1 ± 0.1; interval III–V: 2.4 ± 0.1 and 2.4 ± 0.1. There were no significant differences in ABR parameters between groups 1 and 2 (p > 0.05). Multiple regression analysis showed a slight significant negative correlation between TSH and wave I values (standardized β = −0.267; p = 0.036), without observing any relationship with the other ABR waves recorded.

Conclusions

This study investigated the relationship of TSH and auditory myelinization evaluated by ABR. It did not show a significant change in lower auditory pathway myelinization according to TSH levels in newborns with TSH screening levels lower than 15 μUI/mL.