bluuebunny/crossref_metadata_2025 huggingface dataset:
The pharmacokinetic/pharmacodynamic paradigm for antimicrobial drugs in veterinary medicine: Recent advances and critical appraisal
Authors: Toutain Pierre‐Louis , Pelligand Ludovic , Lees Peter , Bousquet‐Mélou Alain , Ferran Aude A. , Turnidge John D.
Published: October 2020

Pharmacokinetic/pharmacodynamic (PK/PD) modelling is the initial step in the semi‐mechanistic approach for optimizing dosage regimens for systemically acting antimicrobial drugs (AMDs). Numerical values of PK/PD indices are used to predict dose and dosing interval on a rational basis followed by confirmation in clinical trials. The value of PK/PD indices lies in their universal applicability amongst animal species. Two PK/PD indices are routinely used in veterinary medicine, the ratio of the area under the curve of the free drug plasma concentration to the minimum inhibitory concentration (MIC) (fAUC/MIC) and the time that free plasma concentration exceeds the MIC over the dosing interval (fT > MIC). The basic concepts of PK/PD modelling of AMDs were established some 20 years ago. Earlier studies have been reviewed previously and are not reconsidered in this review. This review describes and provides a critical appraisal of more recent, advanced PK/PD approaches, with particular reference to their application in veterinary medicine. Also discussed are some hypotheses and new areas for future developments.First,a brief overview of PK/PD principles is presented as the basis for then reviewing more advanced mechanistic considerations on the precise nature of selected indices. Then, several new approaches to selecting PK/PD indices and establishing their numerical values are reviewed, including (a) the modelling of time–kill curves and (b) the use of population PK investigations. PK/PD indices can be used for dose determination, and they are required to establish clinical breakpoints for antimicrobial susceptibility testing. A particular consideration is given to the precise nature of MIC, because it is pivotal in establishing PK/PD indices, explaining that it is not a “pharmacodynamic parameter” in the usual sense of this term.
Prevalence estimates of voiding disorders in Turkish school‐age children
Authors: Kaplan Fatih , Tabel Yılmaz , Elmas Ahmet Taner
Published: October 2020

Objectives

This study aims to investigate the prevalence of voiding disorders and identify the associated risk factors for school‐age children in East Anatolia, Turkey.

Methods

We randomly selected six primary schools in Malatya in East Anatolia, and 907 students from 6 to 14 years old were involved. Data were obtained using the dysfunctional voiding and incontinence scoring system (DVISS) scale, and children who scored 8.5 or above on that scale were considered as having voiding disorders.

Results

Voiding disorders were detected in 175 (19.2%) of 907 children. One hundred and fifty‐two (16.8%) had day‐time urinary incontinence, and 131 (14.5%) had night‐time incontinence. The findings showed a significant relationship between voiding disorder and daytime/night‐time incontinence, and fecal incontinence. Voiding disorders decreased as the age increased. There was a significant relationship between voiding disorder and positive family history, and the quality of life of these children was significantly affected.

Conclusion

Voiding disorder is a common disease among school‐age children. By identifying and treating voiding disorders and related risk factors in children in the early period, these children can be protected from possible medical or social complications.
Single‐chamber leadless pacemaker for atrial synchronous or ventricular pacing
Authors: Hai Jo‐Jo , Chan Yap‐Hang , Lau Chu‐Pak , Tse Hung‐Fat
Published: October 2020

Leadless pacing is a major breakthrough in the management of bradyarrhythmia. Results of initial clinical trials that have demonstrated a significant reduction in acute and long‐term pacing‐related complications have been confirmed by real‐world experience in a broader spectrum of patients. Nonetheless current use of a leadless pacemaker is hampered by its limited atrial sensing and pacing capability, as well as battery life‐span and retrievability. We review the current clinical outcome data, indications and contraindications, implantation and retrieval techniques, synchronous ventricular pacing, and other clinical considerations. We also provide an overview of the latest advancements in leadless pacing technology including device‐to‐device communication and energy harvesting technology.
Strategies in DNA vaccine for melanoma cancer
Authors: Rezaei Tayebeh , Davoudian Elham , Khalili Saeed , Amini Mohammad , Hejazi Maryam , de la Guardia Miguel , Mokhtarzadeh Ahad
Published: October 2020

According to reports of the international agency for cancer on research, although malignant melanoma shows less prevalence than nonmelanoma skin cancers, it is the major cause of skin cancer mortality. Given that, the production of effective vaccines to control melanoma is eminently required. In this regard, DNA‐based vaccines have been extensively investigated for melanoma therapy. DNA vaccines are capable of inducing both cellular and humoral branches of immune responses. These vaccines possess some valuable advantages such as lack of severe side effects and high stability compared to conventional vaccination methods. The ongoing studies are focused on novel strategies in the development of DNA vaccines encoding artificial polyepitope immunogens based on the multiple melanoma antigens, the inclusion of molecular adjuvants to increase the level of immune responses, and the improvement of delivery approaches. In this review, we have outlined the recent advances in the field of melanoma DNA vaccines and described their implications in clinical trials as a strong strategy in the prevention and control of melanoma.
Development of Acanthocheilonema viteae in Meriones shawi: Absence of microfilariae and production of active ES‐62
Authors: Lumb Felicity E. , Doonan James , Corbet Marlene , Pineda Miguel A. , M. Harnett Margaret , Harnett William
Published: October 2020

Aims

ES‐62 is a well‐studied anti‐inflammatory molecule secreted by L4‐adult stage Acanthocheilonema viteae. We maintain the life cycle of A viteae using Meriones libycus as the definitive host. Here, we investigated whether the full life cycle could be maintained, and functional ES‐62 produced, in a related jird species—Meriones shawi.

Methods and Results

Adult worms were produced in comparable numbers in the two species, but very few microfilariae (MF) were observed in the M shawi bloodstream. M shawi ES‐62 produced ex vivo was functional and protective in a mouse model of arthritis. Myeloid‐derived cells from naïve and infected jirds of both species were compared with respect to ROS production and osteoclast generation, and some differences between the two species in both the absence and presence of infection were observed.

Conclusions

The life cycle of A viteae cannot be successfully completed in M shawi jirds but L3 stage worms develop to adulthood and produce functional ES‐62. Preliminary investigation into jird immune responses suggests that infection can differentially modulate myeloid responses in the two species. However, species‐specific reagents are required to understand the complex interplay between A viteae and its host and to explain the lack of circulating MF in infected M shawi jirds.
Transfusion‐related Epstein‐Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study)
Authors: Enok Bonong Pascal R. , Buteau Chantal , Delage Gilles , Tanner Jerome E. , Lacroix Jacques , Duval Michel , Laporte Louise , Tucci Marisa , Robitaille Nancy , Spinella Philip C. , Cuvelier Geoffrey , Vercauteren Suzanne , Lewis Victor , Fearon Margaret , Drews Steven J , Alfieri Carolina , Trottier Helen
Published: October 2020

Background

Epstein‐Barr virus (EBV) is carried in the blood of most adults, and transfusion‐related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT).

Study Design and Methods

This prospective Canadian multi‐center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV‐negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1).

Results

No statistically significant associations were found between transfusions and EBV. One case of post‐transplant EBV infection was identified among the 21 EBV‐seronegative recipients receiving an EBV‐negative graft. A total of 22 blood donors were retraced to determine whether the recipientʼs EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132‐bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture.

Conclusion

While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.
Trade liberalisation and Chinese firm’s exports: Sourcing from Indonesia
Authors: Ing Lili Yan , Tian Wei , Yu Miaojie
Published: October 2020

We investigate how trade liberalisation affects the performance of Chinese manufacturing firms via sourcing from the South. Taking imports from Indonesia, the largest country in South‐east Asia—China's current trading partner as an example, we find that Chinese firms with higher import shares from Indonesia perform better in productivity, exports and sales, and they are more likely to engage in processing exports. Moreover, the impacts of foreign trade liberalisation on China's export scopes are more pronounced for firms with larger import shares from Indonesia. Such findings are robust to different empirical specifications.
The Problem with ‘Accurate’ History: Complexity within Sallust’s Bellum Catilinae
Authors: Xu Haoyang
Published: October 2020

Sallust’s Bellum Catilinae has long interested historians as one of the few primary accounts of Catiline’s conspiracy and for its complicated portrayal of its protagonist. Rather than depicting Catiline’s conspiracy as either a villainous rebellion or a courageous attempt at revolution, Sallust allows Catiline and his contemporaries to be complex, sometimes contradictory characters in complicated circumstances. In this paper, I begin by suggesting how Sallust nuances Catiline’s character by making him a symptom of widespread decline in the late Roman Republic. I then consider how Sallust’s inclusion of four speeches by Catiline, Caesar, and Cato helps him depict history as complicated by allowing his historical figures to represent their viewpoints in their own persuasive voices. I conclude that Sallust draws attention to the complexity of history in his analysis of Catiline, in order to help his contemporary readers realize the danger that the Republic was facing.
The Social and Cultural Implications of the Egg Freezing Policy in China
Authors: Shao Chenyun
Published: October 2020

The technology of egg freezing has become increasingly popular and has caused heated scholarly debates. However, most scholarships focus on egg freezing exclusively in the United States. This paper fills in the gap by investigating the social and cultural implications of the egg freezing policy in China. This paper first examines feminist rhetoric used by both sides in the global egg freezing debate. The paper then introduces the current Chinese egg freezing policy. This section addresses the question, “Why does the Chinese government implement the current egg freezing policy?” by analyzing how the Chinese culture views reproduction and single women. By analyzing egg freezing in context of the Chinese culture, I concluded that the older and younger generations have different views on egg freezing. Finally, I share the results from a survey that I designed and distributed to see how Chinese people perceive egg freezing. I found that most respondents support universal access to egg freezing in China but have questions on the risks and disadvantages of egg freezing. Many respondents also perceive egg freezing as a technology to “preserve/guarantee motherhood” for women, which ironically serves to pressure women into motherhood instead of giving them true reproductive freedom.
An Orthotic Joint Design for Enhancing Ankle Mobility With Ankle Foot Orthoses Use
Authors: Baker Eileen , Voglewede Philip , Current Thomas , Silver-Thorn Barbara
Published: October 2020

Articulated ankle foot orthoses (AFOs) are prescribed to treat drop-foot, a common neuromuscular weakness observed after a stroke. These assistive devices prevent the toe from dragging during swing (drop-foot) by providing a resistive moment at the ankle. However, existing ankle joint designs for articulated AFOs introduce additional gait pathologies as they also constrain ankle mobility during stance. A novel ankle joint for AFOs to prevent drop-foot during swing and improve ankle mobility during stance was developed, thereby reducing compensatory knee motion during stance. The design intent was to mimic the unconstrained kinematic response of a nonpathologic ankle at initial contact while preventing drop-foot during swing. The design incorporated two modes of operation: locked during swing for support and unlocked during stance for enhanced range of motion. Proof of concept testing with able-bodied subjects was conducted to test walking ability over level ground based on kinetic and kinematic parameters. The comparative tests confirmed the ability of the novel design to prevent drop-foot and its potential for enhanced ankle mobility during stance. Preliminary results indicate that the novel ankle joint should be refined to facilitate smooth and consistent unlocking but can be safely used in its current form with mobility impaired individuals.
Theoretical and Simulation Investigations on Flow Ripple Reduction of Axial Piston Pumps Using Nonuniform Distribution of Pistons
Authors: Lyu Fei , Ye Shaogan , Zhang Junhui , Xu Bing , Huang Weidi , Xu Haogong , Huang Xiaochen
Published: October 2020

The output flow ripple of the axial piston pump is one of the excitation sources for the hydraulic system vibration. The amplitudes of its specific harmonics must be reduced to avoid the resonance with the hydraulic pipeline. In this paper, a method on the nonuniform distribution of the pistons is put forward to adjust the flow ripple. The deflection angles of the pistons are used to describe the distribution rule. The distribution rule is imported to the Fourier expansion of the flow rate of each single-piston chamber, and then every single flow rate is superposed to obtain the Fourier coefficient of total flow rate that becomes the function of deflection angles. After this, objective optimization design is carried out to reduce the amplitudes of specific harmonics. Finally, the dynamic simulation model of the nonuniformly distributed axial piston pump is established to verify the effects of objective optimization. The results show that the amplitude of the ninth harmonic of the flow ripple can be reduced by about 40%, and the reductions are about 99% for the 18th and 27th harmonic.
Elastic Properties and Nonlinear Elasticity of the Noncarbon Hexagonal Lattice Nanomaterials Based on the Multiscale Modeling
Authors: Singh Sandeep , Ravi Raj B. M. , Mali Kiran D. , Watts Gaurav
Published: October 2020

This study presents the elastic properties and nonlinear elasticity of the two-dimensional noncarbon nanomaterials of hexagonal lattice structures having molecular structure XY. Four nitride-based and two phosphide-based two-dimensional nanomaterials, having graphene-like hexagonal lattice structure, are considered in the present study. The four empirical parameters associated with the attractive and repulsive terms of the Tersoff–Brenner potential are calibrated for noncarbon nanomaterials and tested for elastic properties, nonlinear constitutive behavior, bending modulus, bending and torsional energy. The mathematical identities for the tangent constitutive matrix in terms of the interatomic potential function are derived through an atomistic–continuum coupled multiscale framework of the extended version of Cauchy–Born rule. The results obtained using newly calibrated empirical parameters for cohesive energy, bond length, elastic properties, and bending rigidity are compared with those reported in the literature through experimental investigations and quantum mechanical calculations. The continuum approximation is attained through the finite element method. Multiscale evaluations for elastic properties and nonlinear stretching of the nanosheets under in-plane loads are also compared with those obtained from atomistic simulations.
Ultimate Limit State Equations and Plasticity of Tubular Conical Transitions
Authors: Ku Albert , Chen Jieyan
Published: October 2020

Conical transitions have wide applications in wind turbine foundation as well as oil and gas jacket type of structures. The junctions where tubular and cone meet experience a sharp stress rise from shell edge effects. Like all structures experiencing sharp stress rises, fatigue considerations are critical. In addition to fatigue, the existing offshore structural design standards also require ultimate limit state checks. It is known from the lower bound theorem of plasticity limit analysis that the junction local edge effects do not impact the global capacity. Designing for the local junction ultimate limit state contains wide variations among existing design standards. In this paper, the design practices from API RP-2A, NORSOK N-004, and ISO 19902:2020 draft are assessed. They are compared to the shell plastic yield criteria of Hodge and Ilyushin. In addition, this paper provides a semi-analytical plasticity solution to determine junction plastic deformations. The formulation is based on cylindrical shell equations coupled with deformation plasticity theory. It is found that the growth of the junction plasticity zone is limited, which is consistent with the anticipation from the lower bound limit analysis theorem. The observations made in this paper show that the local junction plasticity is a secondary issue compared to other design considerations. Its ultimate limit state design equation can afford to be more lenient if chooses for future standards’ development.
Structural Control of an Ultra-Large Semi-Submersible Floating Offshore Wind Turbine
Authors: Zhao Zhixin , Wang Wenhua , Han Dongdong , Shi Wei , Si Yulin , Li Xin
Published: October 2020

A braceless semi-submersible floating platform is proposed for a Technical University of Denmark (DTU) 10-MW wind turbine at moderate water depths with reference to an existing National Renewable Energy Laboratory (NREL) 5-MW braceless semi-submersible floating platform, and a servo control system for a 10-MW semi-submersible floating offshore wind turbine (FOWT) is introduced. To control the ultimate and fatigue loads of the FOWT, a fore-aft tuned mass damper (TMD) installed in the nacelle of the 10-MW semi-submersible FOWT was investigated for vibration alleviation and load reduction. Considering the hydrodynamic and mooring effect, a four degrees-of-freedom (DOFs) (platform surge and pitch motions, tower fore-aft bending, and TMD translation) simplified dynamic model for the 10-MW semi-submersible FOWT is established based on D’Alembert’s principle. Then, the parameter estimation is conducted based on the Levenberg–Marquardt (LM) algorithm, and the simplified dynamic model was further verified by comparing the output responses with FAST and the proposed model. Furthermore, the exhaustive search (ES) and genetic algorithm (GA) are embedded into the simplified dynamic model to optimize the TMD parameters. Finally, a fully coupled time-domain simulation for all the selected environmental conditions is conducted in FAST, and the vibration suppression performance of the optimized TMD design for the 10-W semi-submersible FOWT was further examined and analyzed.
Advanced NDIF Method for Eigenvalue Analysis of Arbitrarily Shaped Acoustic Cavities With the Partially Pressure-Release Boundary
Authors: Kang S. W. , Atluri Satya N.
Published: October 2020

In this paper, an advanced non-dimensional dynamic influence function method (NDIF method) for eigenvalue analysis of arbitrarily shaped two-dimensional acoustic cavities with the mixed boundary consisting of the pressure-release and rigid-wall boundaries is proposed. The existing NDIF method has the weakness of having to calculate the singularity of the final system matrix of an analyzed acoustic cavity in the frequency band of interest to obtain the eigenvalues of the cavity because the final system matrix is dependent on the frequency. The newly proposed NDIF method in this paper provides an efficient way to extract accurate eigenvalues and eigenmodes by successfully overcoming the above weaknesses. Finally, the validity and accuracy of the proposed method are shown through verification examples.
Global System Reduction Order Modeling for Localized Feature Inclusion
Authors: Quinn D. Dane , Brink Adam R.
Published: October 2020

The development of reduced-order models remains an active research area, despite advances in computational resources. The present work develops a novel order-reduction approach that is designed to incorporate isolated regions that contain, for example, nonlinearitites or accumulating damage. The approach is designed to use global modes of the overall system response, which are then naturally coupled to the response in the isolated region of interest. Two examples are provided to demonstrate both the accuracy and the computational efficiency of the proposed approach. The performance of this approach is compared to the exact response corresponding to a finite element simulation for the chosen problems. In addition, the accuracy and computational efficiency are shown relative to a standard Galerkin reduction based on the linear normal modes. It is found that the proposed reduction offer computational efficiency comparable to a Galerkin reduction, but more accurately represents the response of the system when both are compared to the finite element simulation.
First vaccine may stymie hunt for better ones
Authors: Cohen Jon
Published: October 2020

Should trials keep using placebos once an approved vaccine exists?
Troubles escalate at Ecuador's young research university
Authors: Wessel Lindzi , Ortega Rodrigo Pérez
Published: October 2020

Dozens of professors depart from Yachay Tech amid conflicts that could scuttle its move toward independence.
Social selectivity in aging wild chimpanzees
Authors: Rosati Alexandra G. , Hagberg Lindsey , Enigk Drew K. , Otali Emily , Emery Thompson Melissa , Muller Martin N. , Wrangham Richard W. , Machanda Zarin P.
Published: October 2020

Old chimp friends

As humans age, we prioritize established positive friendships over the new, but risky, socializing we do when we are young. It has been hypothesized that this shift may come as our own sense of mortality kicks in. Rosati
et al.
analyzed a rare, long-term dataset on social bonds among male chimpanzees and found a very similar focus on old and positive friendships (see the Perspective by Silk). Though there is evidence of some sense of time among nonhuman animals, it seems unlikely that they have the same impending sense of mortality that we experience; thus, these results suggest that a different, and deeper, mechanism may be at play.

Science
, this issue p.
473
; see also p.
403
Supertwisted spirals of layered materials enabled by growth on non-Euclidean surfaces
Authors: Zhao Yuzhou , Zhang Chenyu , Kohler Daniel D. , Scheeler Jason M. , Wright John C. , Voyles Paul M. , Jin Song
Published: October 2020

Using curves to make twists

The growth of layered materials on flat substrates usually occurs in stacked layers, although defects or a lattice mismatch can induce strains that distort the shape of subsequent layers. However, these effects are usually small and can be uncontrolled. Zhao
et al.
now demonstrate the possibility of synthesizing multilayers of two-dimensional materials with certain twists between the layers induced by the presence of screw dislocations in combination with curved substrate surfaces. Different twist angles are achieved by varying the amount of nonplanarity and the character (conical or hyperbolic) of the surface.

Science
, this issue p.
442
Polyethylene upcycling to long-chain alkylaromatics by tandem hydrogenolysis/aromatization
Authors: Zhang Fan , Zeng Manhao , Yappert Ryan D. , Sun Jiakai , Lee Yu-Hsuan , LaPointe Anne M. , Peters Baron , Abu-Omar Mahdi M. , Scott Susannah L.
Published: October 2020

A new future for polyethylene

Most current plastic recycling involves chopping up the waste and repurposing it in materials with less stringent engineering requirements than the original application. Chemical decomposition at the molecular level could, in principle, lead to higher-value products. However, the carbon-carbon bonds in polyethylene, the most common plastic, tend to resist such approaches without exposure to high-pressure hydrogen. F. Zhang
et al.
now report that a platinum/alumina catalyst can transform waste polyethylene directly into long-chain alkylbenzenes, a feedstock for detergent manufacture, with no need for external hydrogen (see the Perspective by Weckhuysen).

Science
, this issue p.
437
; see also p.
400
The disruption of divisions
Wall Disease
Jessica Wapner
The Experiment, 2020. 128 pp.
Authors: Díaz-Barriga Miguel , Dorsey Margaret E.
Published: October 2020

Psychological stress is a pervasive aspect of border life, argues a journalist
Saving the poor and vulnerable
Authors: Boyd Ian L.
Published: October 2020

Right now, warm surface water is moving into the western Pacific Ocean in the form of a “La Niña.” It is a sentinel for a complex set of connections that drive weather patterns from the Horn of Africa to Botswana and normally presages drought in East Africa. This event soon will be ringing alarm bells within the World Food Programme (WFP). Even as this United Nations–led agency celebrates its well-deserved award of the 2020 Nobel Peace Prize, the relentless challenge of preventing hunger marches on.
Analytical and Clinical Sample Performance Characteristics of the Onclarity Assay for the Detection of Human Papillomavirus
Authors: Young Stephen , Vaughan Laurence , Yanson Karen , Eckert Karen , Li Aojun , Harris James , Ermel Aaron , Williams James A. , Al-Ghoul Mohammad , Cammarata Catherine L. , Taylor Stephanie N. , Luff Ronald , Cooper Charles K. , Van Der Pol Barbara
Published: October 2020

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV.
Diagnostic Accuracy of the Biosynex CryptoPS Cryptococcal Antigen Semiquantitative Lateral Flow Assay in Patients with Advanced HIV Disease
Authors: Tenforde Mark W. , Boyer-Chammard Timothée , Muthoga Charles , Tawe Leabaneng , Milton Thandi , Rulaganyang Ikanyeng , Lechiile Kwana , Rukasha Ivy , Leeme Tshepo B. , Govender Nelesh P. , Ngidi Julia , Mine Madisa , Molloy Síle F. , Harrison Thomas S. , Lortholary Olivier , Jarvis Joseph N.
Published: October 2020

High cryptococcal antigen (CrAg) titers in blood are associated with subclinical meningitis and mortality in CrAg-positive individuals with advanced HIV disease (AHD). We evaluated a novel semiquantitative lateral flow assay (LFA), CryptoPS, that may be able to identify individuals with high CrAg titers in a cohort of AHD patients undergoing CrAg screening. In a prospective cohort of patients with AHD (CD4 cell count, ≤200/μl) receiving CD4 count testing, whole blood was tested for CrAg by CryptoPS and the IMMY LFA; the two assays were conducted by two different operators, each blind to the results of the other assay.
Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques
Authors: Devasundaram Santhi , Rosati Margherita , Valentin Antonio , Weiss Svenja , Itri Vincenza , Trinh Hung V. , Bear Jenifer , Chowdhury Bhabadeb , LaBranche Celia C. , Montefiori David , Ferrari Guido , Rao Mangala , Kong Xiang-Peng , Zolla-Pazner Susan , Pavlakis George N. , Felber Barbara K.
Published: October 2020

The aim of this work was to design and test a vaccine regimen focusing the immune response on targets associated with infection prevention. We demonstrated that priming with a DNA vaccine expressing only the HIV Env V1V2 region induces Ab responses targeting the critical region in V2 associated with protection. This work shows that V1V2 scaffold DNA priming immunization provides a method to focus immune responses to the desired target region, in the absence of immune interference by other epitopes. This induced immune responses with improved recognition of epitopes important for protective immunity, namely, V2-specific humoral immune responses inversely correlating with HIV risk of infection in the RV144 trial.
Reverse Genetics Approach for Developing Rotavirus Vaccine Candidates Carrying VP4 and VP7 Genes Cloned from Clinical Isolates of Human Rotavirus
Authors: Kanai Yuta , Onishi Misa , Kawagishi Takahiro , Pannacha Pimfhun , Nurdin Jeffery A. , Nouda Ryotaro , Yamasaki Moeko , Lusiany Tina , Khamrin Pattara , Okitsu Shoko , Hayakawa Satoshi , Ebina Hirotaka , Ushijima Hiroshi , Kobayashi Takeshi
Published: October 2020

Although vaccines have reduced global RV-associated hospitalization and mortality over the past decade, the multisegmented genome of RVs allows reassortment of VP4 and VP7 genes from different RV species and strains. The evolutionary dynamics of novel RV genotypes and their constellations have led to great genomic and antigenic diversity. The reverse genetics system is a powerful tool for manipulating RV genes, thereby controlling viral antigenicity, growth capacity, and pathogenicity. Here, we generated recombinant simian RVs (strain SA11) carrying heterologous VP4 and VP7 genes cloned from clinical isolates and showed that VP4- or VP7-substituted chimeric viruses can be used for antigenic characterization of RV outer capsid proteins and as improved seed viruses for vaccine production.
Simian-Human Immunodeficiency Virus SHIV.C.CH505 Persistence in ART-Suppressed Infant Macaques Is Characterized by Elevated SHIV RNA in the Gut and a High Abundance of Intact SHIV DNA in Naive CD4
+
T Cells
Authors: Obregon-Perko Veronica , Bricker Katherine M. , Mensah Gloria , Uddin Ferzan , Kumar Mithra R. , Fray Emily J. , Siliciano Robert F. , Schoof Nils , Horner Anna , Mavigner Maud , Liang Shan , Vanderford Thomas , Sass Julian , Chan Cliburn , Berendam Stella J. , Bar Katharine J. , Shaw George M. , Silvestri Guido , Fouda Genevieve G. , Permar Sallie R. , Chahroudi Ann
Published: October 2020

Uncovering the sanctuaries of the long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity is distinct from that of adults, which may alter where the reservoir is established in infancy. Thus, it is important to utilize pediatric models to inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model of HIV-1 infection via breastfeeding to identify key sites of viral persistence under antiretroviral therapy (ART). The gastrointestinal tract was found to be a site for low-level viral transcription during ART. We also show that naive CD4
+
T cells harbored intact provirus and were a major contributor to blood and lymphoid reservoir size. This is particularly striking, as memory CD4
+
T cells are generally regarded as the main source of latent HIV/simian immunodeficiency virus (SIV) infection of adult humans and rhesus macaques. Our findings highlight unique features of reservoir composition in pediatric infection that should be considered for eradication efforts.
The NSs Protein Encoded by the Virulent Strain of Rift Valley Fever Virus Targets the Expression of Abl2 and the Actin Cytoskeleton of the Host, Affecting Cell Mobility, Cell Shape, and Cell-Cell Adhesion
Authors: Bamia Aline , Marcato Vasco , Boissière Magali , Mansuroglu Zeyni , Tamietti Carole , Romani Mattea , Simon Dominique , Tian Guanfang , Niedergang Florence , Panthier Jean-Jacques , Flamand Marie , Souès Sylvie , Bonnefoy Eliette
Published: October 2020

Rift Valley fever virus (RVFV) is a dangerous human and animal pathogen that was ranked by the World Health Organization in 2018 as among the eight pathogens of most concern for being likely to cause wide epidemics in the near future and for which there are no, or insufficient, countermeasures. The focus of this work is to address the question of the mechanisms underlying RVFV-induced cytopathic effects that participate in RVFV pathogenicity. We demonstrate here that RVFV targets cell adhesion and the actin cytoskeleton at the transcriptional and cellular level, affecting cell mobility and inducing cell shape collapse, along with distortion of cell-cell adhesion. All these effects may participate in RVFV-induced pathogenicity, facilitate virulent RVFV dissemination, and thus constitute interesting potential targets for future development of antiviral therapeutic strategies that, in the case of RVFV, as with several other emerging arboviruses, are presently lacking.
Diagnosis of oesophageal mucormycosis managed with medical therapy alone
Authors: Ringer Matthew , Pischel Lauren , Azar Marwan Mikheal
Published: October 2020

Mucormycosis is an invasive mould that can cause aggressive infection, particularly in immunocompromised patients. Though oesophageal mucormycosis is relatively rare, it remains an elusive and devastating manifestation of this disease. The management is also challenging, due to surgical morbidity and contraindications such as thrombocytopenia in immunocompromised hosts. In this report, we present the case of a 60-year-old Lebanese man with newly diagnosed acute myeloid leukaemia who developed oesophageal mucormycosis after induction chemotherapy with idarubicin/cytarabine (7+3). The diagnosis was made when the patient developed febrile neutropenia and odynophagia. CT scan of the chest revealed a thickened oesophagus. Oesophagogastroduodenoscopy with biopsy, histopathology and PCR were performed, resulting in the diagnosis ofRhizopus microsporus. The patient was successfully treated with liposomal amphotericin B and salvage posaconazole therapy without surgical intervention. We reviewed the clinical characteristics of the six published oesophageal mucormycosis reports from the literature.
Benefits of medication charts provided at transitions of care: a narrative systematic review
Authors: Dietrich Fine Michèle , Hersberger Kurt E , Arnet Isabelle
Published: October 2020

Objectives

Particularly at transitions of care points information concerning current medication tends to be incomplete. A medication chart that contains all essential information on current therapy is likely to be a helpful tool for patients and healthcare providers. We aimed to investigate any type of benefits associated with medication charts provided at transition points.

Methods

A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases, two online journals and two association websites dedicated to biomedicine and pharmacy issues were consulted to identify studies for the review using the search term ‘medication chart’ and synonyms. We run our search from database inception up to March 2019. Studies of any study design, intervention and population which examined the effect of paper-based medication charts were included. We extracted study results narratively and coded and classified them by themes and categories inductively by using the ‘framework method’ with content analysis. The methodological quality of the studies was assessed using the Effective Public Health Practice Project (EPHPP) tool.

Results

From the 846 retrieved articles, 30 studies met the inclusion criteria, mostly from Germany (18 studies) and the USA (5 studies). Thirteen studies reported a statistically significant result. In the ‘patient theme’, the most obvious benefits were an increase in medication knowledge, a reduction of medication errors and higher medication adherence. In the ‘interdisciplinary theme’, a medication chart represented a helpful tool to increase communication and inter-sectoral cooperation between healthcare providers. In the ‘theme of terms and conditions’, accuracy and currency of data are prerequisites for any positive effect. The quality of the studies was classified predominantly weak mainly due to unmet good quality criteria (no randomised controlled trials study design, no reported dropouts).

Conclusion

Overall, the reviewed studies suggested some benefits when using medication charts. Healthcare providers could consider using medication charts in their counselling practice. However, it is unknown whether the reported benefits lead to measurable improvement in clinical outcomes.

PROSPERO registration number
The role of concomitant ligament injury in the development of post-traumatic osteoarthritis after distal radius fractures: a protocol for a systematic review
Authors: Slichter Malou E , Kraan Gerald A , Bramer Wichor M , Colaris Joost W , Mathijssen Nina M C
Published: October 2020

Introduction

Treatment of distal radius fractures (DRFs) aims to restore anatomic position of the fracture fragments and congruity of the articular surface to optimise functional outcomes and prevent osteoarthritis in the long term. While ligament injury of the wrist is often associated with DRFs and sole ligament injuries of the wrist lead to osteoarthritis, it is plausible that concomitant ligament injury in DRFs may aggravate degenerative changes of the wrist. The relationship between concomitant ligament injury and post-traumatic osteoarthritis in patients with DRFs is unclear. This study aims to identify the types of associated ligament injury in patients with a DRF and to elucidate the association of ligament injury on the development of post-traumatic osteoarthritis.

Methods and analysis

This protocol is written in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. An electronic search in MEDLINE, Embase, Web of Science, Cochrane Central Register of Trials and Google Scholar has been created and performed by a Health Sciences librarian with expertise in systematic review searching. Original research articles in English literature, which report on concomitant ligament injury of the wrist in relation to post-traumatic osteoarthritis, patient-reported outcome measures or clinician-reported outcome measures in patients (aged ≥18 years) with DRFs will be included. Two reviewers will independently screen and appraise articles and perform data extraction. In case of any disagreements, a third reviewer will be consulted. A systematic qualitative synthesis will be performed using text and tables.

Ethics and dissemination

No ethical approval is required, since this is a protocol for a systematic review. The systematic review will be submitted for publication in a peer-reviewed scientific journal and for presentation at relevant conferences.

PROSPERO registration number

CRD42020165007.
Management and early outcomes of children with appendicitis in the UK and Ireland during the COVID-19 pandemic: a survey of surgeons and observational study
Authors: Bethell George S , Rees Clare M , Sutcliffe Jonathan R , Hall Nigel J
Published: October 2020

Objectives

Acute appendicitis is the most common surgical condition in children. In the UK, appendicectomy is the most common treatment with non-operative management unusual. Due to concerns about the risk of SARS-CoV-2 transmission during surgical procedures, surgeons were advised to consider non-operative treatment and avoid laparoscopy where possible. This study aims to report management and outcomes, to date, of children with appendicitis in the UK and Ireland during the COVID-19 pandemic.

Design

Survey of consultant surgeons who treat children with appendicitis that informed a prospective multicentre observational cohort study.

Setting

Data were collected from centres in the UK and Ireland for cases admitted between 1 April and 31 May 2020 (first 2 months of the COVID-19 pandemic) at both general surgical and specialist paediatric surgical centres.

Participants

The study cohort includes 838 children with a clinical and/or radiological diagnosis of acute appendicitis of which 527 (63%) were male.

Main outcomes measured

Primary outcome was treatment strategy used for acute appendicitis. Other outcomes reported include change in treatment strategy over time, use of diagnostic imaging and important patient outcomes to 30 days following hospital admission.

Results

From very early in the pandemic surgeons experienced a change in their management of children with appendicitis and almost all surgeons who responded to the survey anticipated further changes during the pandemic. Overall, 326/838 (39%) were initially treated non-operatively of whom 81/326 (25%) proceeded to appendicectomy within the initial hospital admission. Of cases treated initially surgically 243/512 (48%) were performed laparoscopically. Diagnostic imaging was used in 445/838 (53%) children. Cases treated non-operatively had a shorter hospital stay than those treated surgically but hospital readmissions within 30 days were similar between groups. In cases treated surgically the negative appendicectomy rate was 4.5%. There was a trend towards increased use of surgical treatment and from open to laparoscopic appendicectomy as the pandemic progressed.

Conclusion

Non-operative treatment of appendicitis has been widely used for the first time in children in the UK and Ireland and is safe and effective in selected patients. Overall patient outcomes do not appear to have been adversely impacted by change in management during the pandemic thus far.
Abortion regulation in Europe in the era of COVID-19: a spectrum of policy responses
Authors: Moreau Caroline , Shankar Mridula , Glasier Anna , Cameron Sharon , Gemzell-Danielsson Kristina
Published: October 2020

Background

Unprecedented public health actions restricting movement and non-COVID related health services are likely to have affected abortion care during the pandemic in Europe. In the absence of a common approach to ensure access to this essential health service, we sought to describe the variability of abortion policies during the outbreak in Europe in order to identify strategies that improve availability and access to abortion in times of public health crises.

Methods

We collected information from 46 countries/regions: 31 for which country-experts completed a survey and 15 for which we conducted a desk review. We describe abortion regulations and changes to regulations and practice during the pandemic.

Results

During COVID-19, abortions were banned in six countries and suspended in one. Surgical abortion was less available due to COVID-19 in 12 countries/regions and services were not available or delayed for women with COVID-19 symptoms in eleven. No country expanded its gestational limit for abortion. Changes during COVID-19, mostly designed to reduce in-person consultations, occurred in 13 countries/regions. Altogether eight countries/regions provided home medical abortion with mifepristone and misoprostol beyond 9 weeks (from 9 weeks+6 days to 11 weeks+6 days) and 13 countries/regions up to 9 weeks (in some instances only misoprostol could be taken at home). Only six countries/regions offered abortion by telemedicine.

Conclusions

The lack of a unified policy response to COVID-19 restrictions has widened inequities in abortion access in Europe, but some innovations including telemedicine deployed during the outbreak could serve as a catalyst to ensure continuity and equity of abortion care.
Trends and disparities in American Indian/Alaska Native unintentional injury mortality from 1999 to 2016
Authors: Kerr William C , Ye Yu , Williams Edwina , Mulia Nina , Cherpitel Cheryl J
Published: October 2020

Introduction

Alcohol and drug use are significant problems in the US, and American Indian/Alaska Native (AI/AN) communities and individuals are known to be among the most affected. This study evaluates disparities in unintentional injury mortality causes since 1999.

Methods

Analyses in 2020 of unintentional injury mortality rate disparities between AI/ANs and white population over the 1999–2016 period with attention to motor vehicle crashes, alcohol poisoning, drug poisoning and all other cause types. Rates in each of the 10 states with the largest AI/AN populations were also investigated to account for geographical concentration.

Results

Motor vehicle mortality rates declined for both AI/AN and white groups, but a large racial disparity was maintained. Conversely, poisoning mortality rates rose substantially in both groups, with a jump in rates in 2007 due to a coding change, resulting in a large disparity that was maintained through 2016. Comparison of alcohol and drug poisonings showed that the AI/AN alcohol poisoning rate was about eight times the white rate, whereas drug poisoning rates were similar. For ‘all other’ unintentional injuries, the highest rates were seen for AI/AN men, with rates generally rising over the study period. State-specific analyses found substantial variation in AI/AN rates, with few or no disparities in New York and Texas.

Conclusions

Results indicate substantial and persisting disparities in unintentional injury mortality, with especially large differences in alcohol poisoning. The absence of disparities in New York and Texas suggest the importance of situational factors.
Making emergency responders visible: working-class responses to industrial disaster in 19th-century journalism and poetry
Authors: Buckland Rosalyn
Published: October 2020

Hidden beneath the ground in coalmines, or behind the walls of factories, injured bodies of workers have too often been overlooked. Using the 1842 Hartley Colliery disaster as a case study, this paper contrasts journalistic neglect with the ways in which working-class poets illuminated responses to large-scale injury. Often the greatest difficulty in industrial disaster was in securing access to trapped victims. Arriving late on the scene, neither journalists nor doctors were able to influence the outcome of events: in most cases emergency treatment was provided by workers themselves. While journalists struggled to portray these men’s stories, working-class poets such as Joseph Skipsey brought attention to their collaborative actions even in the face of injury or death. The actions of these colliers as first responders had a lasting significance, foreshadowing working-class involvement in the wider cultural shift towards collective responsibility for healthcare.