bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Polythiourea-Copper Complex Composite Membrane and its Anti-fouling Property
Authors: Margarito M T , Beltran A B , Promentilla MA , Orbecido A , Basilia B , Damalerio R , Bigol U
Published: May 2020

A Composite Flat Sheet Membrane Containing Polythiourea-Copper (PTU-Cu) Complex was fabricated through a two-step phase separation involving complexation and/or crosslinking of the polymer by copper ions (Cu2+) on the first step and non-solvent induced phase separation on the second step. The surface topography of the membrane was analysed using Atomic Force Microscope (AFM) in non-contact mode. The incorporation of copper at the surface was confirmed through Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX) mapping wherein other elements such as Sulfur (S), Carbon (C) and Oxygen (O) of the polymer were conducted. The fabricated membrane was rigid as shown by high value (about 2.15 GigaPascal) of measured Young’s modulus using the Pinpoint Nanomechanical Analysis Mode of AFM. In addition, the surface charge and hydrophobicity were measured using the Electrostatic Force Microscope (EFM) and water contact angle respectively. The antifouling characteristics of the membrane was evaluated through antimicrobial membrane surface contact test wherein E. coli was used as test microorganism. Other membrane properties such as pore size distribution and pure water flux were measured using a porometer and a filtration apparatus.
Functional evaluation of prevascularization in one-stage versus two-stage tissue engineering approach of human bio-artificial muscle
Authors: Gholobova D , Terrie L , Mackova K , Desender L , Carpentier G , Gerard M , Hympanova L , Deprest J , Thorrez L
Published: May 2020

A common shortcoming of current tissue engineered constructs is the lack of a functional vasculature, limiting their size and functionality. Prevascularization is a possible strategy to introduce vascular networks in these constructs. It includes among others co-culturing target cells with endothelial (precursor) cells that are able to form endothelial networks through vasculogenesis. In this paper, we compared two different prevascularization approaches of bio-artificial skeletal muscle tissue (BAM) in vitroandin vivo. In a one-stage approach, human muscle cells were directly co-cultured with endothelial cells in 3D. In a two-stage approach, a one week old BAM containing differentiated myotubes was coated with a fibrin hydrogel containing endothelial cells. The obtained endothelial networks were longer and better interconnected with the two-stage approach. We evaluated whether prevascularization had a beneficial effect onin vivoperfusion of the BAM and improved myotube survival by implantation on the fascia of thelatissimus dorsimuscle of NOD/SCID mice for 5 or 14 d. Alsoin vivo, the two-stage approach displayed the highest vascular density. At day 14, anastomosis of implanted endothelial networks with the host vasculature was apparent. BAMs without endothelial networks contained longer and thicker myotubesin vitro, but their morphology degradedin vivo. In contrast, maintenance of myotube morphology was well supported in the two-stage prevascularized BAMs. To conclude, a two-stage prevascularization approach for muscle engineering improved the vascular density in the construct and supported myotube maintenancein vivo.
Reactive cavitation erosion as a technique for production of functionalized copper hydroxychloride nanomaterials
Authors: Wright Jeremy W , Mitchell Brian S
Published: May 2020

The production of functionalized clinoatacamite (Cu2(OH)3Cl) nanoparticles from Reactive Cavitation Erosion (RCE) of copper in 1 M aqueous guanidine hydrochloride (GHCl) solution was investigated for applications as potential quantum magnet materials. As-synthesized nanomaterial was characterized by Diffuse-Reflectance Infrared Fourier-Transform Spectroscopy (DRIFTS), XRD, and TEM. These analyses were compared to nanoparticles produced from RCE of Cu in KCl and RCE of Cu in GHCl in oxygen-depleted (Ar) and oxygen-rich (compressed air, CA) solutions to identify possible reaction pathways.
Anti-arbitration injunctions: walking the tightrope
Authors: Garnett Richard
Published: May 2020

Anti-arbitration injunctions are a controversial issue in the field of international arbitration. While some commentators decry them as an interference with the autonomy and independence of arbitrators, English and other common law courts steadfastly refuse to renounce them entirely. By reference to the framework established in recent decisions of the English Court of Appeal, the article seeks to forge a middle path between making anti-arbitration injunctions available on a discretionary, case management basis and prohibiting them in all cases. An approach that respects both the rights of arbitrators to determine their own jurisdiction and the rights of courts to protect parties from abuse of the arbitral process is advocated.
Loss of TMEM106B leads to myelination deficits: implications for frontotemporal dementia treatment strategies
Authors: Zhou Xiaolai , Nicholson Alexandra M , Ren Yingxue , Brooks Mieu , Jiang Peizhou , Zuberi Aamir , Phuoc Hung Nguyen , Perkerson Ralph B , Matchett Billie , Parsons Tammee M , Finch NiCole A , Lin Wenlang , Qiao Wenhui , Castanedes-Casey Monica , Phillips Virginia , Librero Ariston L , Asmann Yan , Bu Guojun , Murray Melissa E , Lutz Cathleen , Dickson Dennis W , Rademakers Rosa
Published: May 2020

Genetic variants that define two distinct haplotypes at the TMEM106B locus have been implicated in multiple neurodegenerative diseases and in healthy brain ageing. In frontotemporal dementia (FTD), the high expressing TMEM106B risk haplotype was shown to increase susceptibility for FTD with TDP-43 inclusions (FTD-TDP) and to modify disease penetrance in progranulin mutation carriers (FTD-GRN). To elucidate the biological function of TMEM106B and determine whether lowering TMEM106B may be a viable therapeutic strategy, we performed brain transcriptomic analyses in 8-month-old animals from our recently developed Tmem106b−/− mouse model. We included 10 Tmem106b+/+ (wild-type), 10 Tmem106b+/− and 10 Tmem106−/− mice. The most differentially expressed genes (153 downregulated and 60 upregulated) were identified between Tmem106b−/− and wild-type animals, with an enrichment for genes implicated in myelination-related cellular processes including axon ensheathment and oligodendrocyte differentiation. Co-expression analysis also revealed that the most downregulated group of correlated genes was enriched for myelination-related processes. We further detected a significant loss of OLIG2-positive cells in the corpus callosum of Tmem106b−/− mice, which was present already in young animals (21 days) and persisted until old age (23 months), without worsening. Quantitative polymerase chain reaction revealed a reduction of differentiated but not undifferentiated oligodendrocytes cellular markers. While no obvious changes in myelin were observed at the ultrastructure levels in unchallenged animals, treatment with cuprizone revealed that Tmem106b−/− mice are more susceptible to cuprizone-induced demyelination and have a reduced capacity to remyelinate, a finding which we were able to replicate in a newly generated Tmem106b CRISPR/cas9 knock-out mouse model. Finally, using a TMEM106B HeLa knock-out cell line and primary cultured oligodendrocytes, we determined that loss of TMEM106B leads to abnormalities in the distribution of lysosomes and PLP1. Together these findings reveal an important function for TMEM106B in myelination with possible consequences for therapeutic strategies aimed at lowering TMEM106B levels.
Focal Electrical Stimulation of Cortical Functional Networks
Authors: Hu Jia Ming , Qian Mei Zhen , Tanigawa Hisashi , Song Xue Mei , Roe Anna Wang
Published: May 2020

Traditional electrical stimulation of brain tissue typically affects relatively large volumes of tissue spanning multiple millimeters. This low spatial resolution stimulation results in nonspecific functional effects. In addition, a primary shortcoming of these designs was the failure to take advantage of inherent functional organization in the cerebral cortex. Here, we describe a new method to electrically stimulate the brain which achieves selective targeting of single feature-specific domains in visual cortex. We provide evidence that this paradigm achieves mesoscale, functional network-specificity, and intensity dependence in a way that mimics visual stimulation. Application of this approach to known feature domains (such as color, orientation, motion, and depth) in visual cortex may lead to important functional improvements in the specificity and sophistication of brain stimulation methods and has implications for visual cortical prosthetic design.
Optimization of Extraction Conditions of Continentalic and Kaurenoic Acids from Aralia continentalis by HPLC/UV and Their Validation
Authors: Lee Ju Sung , Quilantang Norman G , Hahm Dae-Hyun , Kang Ki Sung , Jacinto Sonia D , Choi Yu-Jin , Lee Sang Cheon , Lee Sanghyun
Published: May 2020

Aralia continentalis (AC) is a perennial herb that has long been used as a traditional medicine for many diseases. Continentalic acid (CA) and kaurenoic acid (KA) are major diterpenoids in AC, which are known to exert various pharmacological activities. This study focuses on the optimization of the extraction of CA and KA from dried AC roots by evaluating the influence of different extraction conditions on their yield. Five extraction variables were examined: sample weight, solvent concentration, extraction time, solid matrix and the number of repeated extractions. The analytical method used in this study was also validated in terms of linearity, limit of detection, limit of quantification, precision and accuracy. The CA and KA yields were measured by high-performance liquid chromatography analysis. The results show that CA and KA were the highest when unpulverized samples (3.75 g) were subjected to a single extraction for 5 h using 50% ethanol (300 mL) as the solvent. These conditions are proposed for the optimization of the extraction of CA and KA from AC.
Economic Considerations in Infectious Diseases Emergency Response Preparedness: It’s All About the Point of View
Authors: Branch-Elliman Westyn , Safdar Nasia , Nelson Richard
Published: May 2020

Outbreaks and emergence of novel pathogens present a challenge in economic evaluations of prevention strategies, due to unusually high levels of risk aversion and uncertainty. Here, we discuss cost-effectiveness investigations and interpretation of economic analyses in the context of outbreak planning and containment, and outline considerations for providers, administrators, patients, and policy makers for infection emergency preparedness response.
Pulsed Levosimendan in advanced heart failure due to congenital heart disease: a case series
Authors: Cranley James , Hardiman Antonia , Freeman Leisa J
Published: May 2020

Background

Levosimendan is a non-adrenergic calcium-sensitizing agent with positive inotropic and vasodilatory effects. Its use in acute decompensation of heart failure is established. Good evidence now exists for repetitive infusions of Levosimendan to improve symptoms and reduce hospitalization in advanced heart failure (AdHF) populations. Its use in heart failure resulting from congenital heart disease is not yet commonplace.

Case summary

We present three cases in which pulsed Levosimendan was used in the management of AdHF secondary to underlying congenital heart disease. There was symptomatic and biomarker evidence of improvement.

Discussion

Intermittent Levosimendan may represent a valuable therapy to reduce hospitalization and improve quality of life in adults with congenital heart conditions.
The Social Costs of Side Trading
Authors: Attar Andrea , Mariotti Thomas , Salanié François
Published: May 2020

We study resource allocation under private information when the planner cannot prevent bilateral side trading between consumers and firms. Adverse selection and side trading severely restrict feasible trades: each marginal quantity must be fairly priced given the consumer types who purchase it. The resulting social costs are twofold. First, second-best efficiency and robustness to side trading are in general irreconcilable requirements. Second, there actually exists only one budget-feasible allocation robust to side trading, which deprives the planner from any capacity to redistribute resources between different types of consumers. We discuss the relevance of our results for insurance and financial markets.
C. Wilfred Jenks and the Futures of International Organizations Law
Authors: Sinclair Guy Fiti
Published: May 2020

This article situates C. Wilfred Jenks as a central figure in the emergence and development of the law of international organizations. Deeply informed by his work as a legal advisor at the International Labour Organization (ILO), Jenks’ scholarly writings during and immediately after World War II established a basis for, and elaborated the details of many aspects of, classical international organizations law. Moreover, the article argues that Jenks’ oeuvre also articulated a number of insights and approaches that, in retrospect, may be read as suggesting a series of alternative futures for international organizations law. By examining Jenks’ foundational works on international organizations law, therefore, the article seeks to recover aspects of Jenks’ thinking that might have led – and might still lead – the field to explore different paths.
Substrate-dependent CO2 fixation in heterotrophic bacteria revealed by stable isotope labelling
Authors: Spona-Friedl Marina , Braun Alexander , Huber Claudia , Eisenreich Wolfgang , Griebler Christian , Kappler Andreas , Elsner Martin
Published: May 2020

Virtually all heterotrophs incorporate carbon dioxide by anaplerotic fixation. Little explored, however, is the interdependency of pathways and rates of CO2fixation on the concurrent usage of organic substrate(s). Potentially, this could reveal which substrates out of a pool of dissolved organic carbon are utilised by environmental microorganisms. To explore this possibility, Bacillus subtilis W23 was grown in a minimal medium with normalised amounts of either glucose, lactate or malate as only organic substrates, each together with 1 g/L NaH13CO3. Incorporation of H13CO3− was traced by elemental analysis-isotope ratio mass spectrometry of biomass and gas chromatography-mass spectrometry of protein-derived amino acids. Until the late logarithmic phase, 13C incorporation into the tricarboxylic acid cycle increased with time and occurred via [4–13C]oxaloacetate formed by carboxylation of pyruvate. The levels of 13C incorporation were highest for growth on glucose and lowest on malate. Incorporation of 13C into gluconeogenesis products was mainly detected in the lactate and malate experiment, whereas glucose down-regulated this path. A proof-of-principle study with a natural groundwater community confirmed the ability to determine incorporation from H13CO3− by natural communities leading to specific labelling patterns. This underlines the potential of the labelling approach to characterise carbon sources of heterotrophic microorganisms in their natural environments.
Experimental assembly reveals ecological drift as a major driver of root nodule bacterial diversity in a woody legume crop
Authors: Ramoneda Josep , Le Roux Johannes J , Frossard Emmanuel , Frey Beat , Gamper Hannes Andres
Published: May 2020

Understanding how plant-associated microbial communities assemble and the role they play in plant performance are major goals in microbial ecology. For nitrogen-fixing rhizobia, community assembly is generally driven by host plant selection and soil conditions. Here, we aimed to determine the relative importance of neutral and deterministic processes in the assembly of bacterial communities of root nodules of a legume shrub adapted to extreme nutrient limitation, rooibos (Aspalathus linearis Burm. Dahlgren). We grew rooibos seedlings in soil from cultivated land and wild habitats, and mixtures of these soils, sampled from a wide geographic area, and with a fertilization treatment. Bacterial communities were characterized using next generation sequencing of part of the nodA gene (i.e. common to the core rhizobial symbionts of rooibos), and part of the gyrB gene (i.e. common to all bacterial taxa). Ecological drift alone was a major driver of taxonomic turnover in the bacterial communities of root nodules (62.6% of gyrB communities). In contrast, the assembly of core rhizobial communities (genus Mesorhizobium) was driven by dispersal limitation in concert with drift (81.1% of nodA communities). This agrees with a scenario of rooibos-Mesorhizobium specificity in spatially separated subpopulations, and low host filtering of other bacteria colonizing root nodules in a stochastic manner.
Rhinovirus impairs the immune response of alveolar macrophages to facilitate Streptococcus pneumonia infection
Authors: Wei Huiping , Zhao Hui , Li Ruifang , Yang Feiyun , Wu Yan
Published: May 2020

Pneumonia is one important cause of mortality in neonates. However, the mechanism remains still unclear. Viral infection greatly enhances the morbidity of Streptococcus pneumonia. In this study, we tried to understand how human rhinovirus (HRV) would accelerate Streptococcus pneumonia infection. Alveolar macrophages (AMs) were isolated from neonatal mice. Cytokine concentrations were detected using ELISA. The phagocytosis of Streptococcus pneumonia by AMs was indicated by immunofluorescence. Toll-like receptor 3 (TLR3) and CD68 expression in isolated AMs or infected mice were determined by western blot or immunochemistry. The mortality was explored using Kaplan–Meier analysis. HRV infection enhanced cytokine release by AMs, and decreased Streptococcus pneumonia-induced TNF-α, IL-1β and IL-6 release by AMs, while has no influence on IL-10 release. HRV infection impaired phagocytosis of Streptococcus pneumonia in AMs. Mechanically, HRV infection up-regulated TLR3 expression in AMs. Mortality and pneumococcal burden decreased in TLR3−/− neonatal mice and inflammation and phagocytosis were restored in TLR3−/− AMs. Neonatal rhinovirus impairs the immune response of alveolar macrophages to facilitate Streptococcus pneumonia infection via TLR3 signaling.
The Protector within: Comparative Genomics of APSE Phages across Aphids Reveals Rampant Recombination and Diverse Toxin Arsenals
Authors: Rouïl Jeff , Jousselin Emmanuelle , Coeur d’acier Armelle , Cruaud Corinne , Manzano-Marín Alejandro
Published: May 2020

Phages can fundamentally alter the physiology and metabolism of their hosts. Although these phages are ubiquitous in the bacterial world, they have seldom been described among endosymbiotic bacteria. One notable exception is the APSE phage that is found associated with the gammaproteobacterial Hamiltonella defensa, hosted by several insect species. This secondary facultative endosymbiont is not necessary for the survival of its hosts but can infect certain individuals or even whole populations. Its infection in aphids is often associated with protection against parasitoid wasps. This protective phenotype has actually been linked to the infection of the symbiont strain with an APSE, which carries a toxin cassette that varies among so-called “types.” In the present work, we seek to expand our understanding of the diversity of APSE phages as well as the relations of their Hamiltonella hosts. For this, we assembled and annotated the full genomes of 16 APSE phages infecting Hamiltonella symbionts across ten insect species. Molecular and phylogenetic analyses suggest that recombination has occurred repeatedly among lineages. Comparative genomics of the phage genomes revealed two variable regions that are useful for phage typing. Additionally, we find that mobile elements could play a role in the acquisition of new genes in the toxin cassette. Altogether, we provide an unprecedented view of APSE diversity and their genome evolution across aphids. This genomic investigation will provide a valuable resource for the design and interpretation of experiments aiming at understanding the protective phenotype these phages confer to their insect hosts.
Magnitude distribution complexity and variation at The Geysers geothermal field
Authors: Leptokaropoulos Konstantinos
Published: May 2020

Earthquake magnitude (size) distribution is a major component required for seismic hazard assessment and therefore, the accurate determination of its functional shape and variation is a task of utmost importance. Although often considered as stationary, the magnitude distribution at particular sites may significantly vary over time and space. In this study, the well-known Gutenberg–Richter (GR) law, which is widely assumed to describe earthquake magnitude distribution, is tested for a case study of seismicity induced by fluid injection at The Geysers (CA, USA) geothermal field. Statistical tests are developed and applied in order to characterize the magnitude distribution of a high quality catalogue comprising seismicity directly associated with two injection wells, at the north western part of The Geysers. The events size distribution variation is investigated with respect to spatial, temporal, fluid injection and magnitude cut-off criteria. A thorough spatio-temporal analysis is performed for defining seismicity Clusters demonstrating characteristic magnitude distributions which significantly differ from the ones of the nearby Clusters. The magnitude distributions of the entire seismic population as well as of the individual Clusters are tested for their complexity in terms of exponentiality, multimodal and multibump structure. Then, the Clusters identified are further processed and their characteristics are determined in connection to injection rate fluctuations. The results of the analysis clearly indicate that the entire magnitude distribution is definitely complex and non-exponential, whereas subsequent periods demonstrating significantly diverse magnitude distributions are identified. The regional seismicity population is divided into three major families, for one of which exponentiality of magnitude distribution is clearly rejected, whereas for the other two the GR law b-value is directly proportional to fluid injection. In addition, the b-values of these Families seem to be significantly magnitude dependent, a fact that is of major importance for seismic hazard assessment implementations. To conclude, it is strongly suggested that magnitude exponentiality must be tested before proceeding to any b-value calculations, particularly in anthropogenic seismicity cases where complex and time changeable processes take place.
The distinctive roles of urban community health workers in low- and middle-income countries: a scoping review of the literature
Authors: Ludwick Teralynn , Morgan Alison , Kane Sumit , Kelaher Margaret , McPake Barbara
Published: May 2020

Addressing urban health challenges in low- and middle-income countries (LMICs) has been hampered by lack of evidence on effective mechanisms for delivering health services to the poor. The urban disadvantaged experience poor health outcomes (often worse than rural counterparts) and face service barriers. While community health workers (CHWs) have been extensively employed in rural communities to address inequities, little attention has been given to understanding the roles of CHWs in urban contexts. This study is the first to systematically examine urban CHW roles in LMICs. It aims to understand their roles vis-à-vis other health providers and raise considerations for informing future scope of practice and service delivery models. We developed a framework that presents seven key roles performed by urban CHWs and position these roles against a continuum of technical to political functions. Our scoping review included publications from four databases (MEDLINE, EMBASE, CINAHL and Social Sciences Citation Index) and two CHW resource hubs. We included all peer-reviewed, CHW studies situated in urban/peri-urban, LMIC contexts. We identify roles (un)commonly performed by urban CHWs, present the range of evidence available on CHW effectiveness in performing each role and identify considerations for informing future roles. Of 856 articles, 160 met the inclusion criteria. Programmes spanned 34 LMICs. Studies most commonly reported evidence on CHWs roles related to health education, outreach and elements of direct service provision. We found little overlap in roles between CHWs and other providers, with some exceptions. Reported roles were biased towards home visiting and individual-capacity building, and not well-oriented to reach men/youth/working women, support community empowerment or link with social services. Urban-specific adaptations to roles, such as peer outreach to high-risk, stigmatized communities, were limited. Innovation in urban CHW roles and a better understanding of the unique opportunities presented by urban settings is needed to fully capitalize on their potential.
Assessing County-Level Vulnerability for Opioid Overdose and Rapid Spread of Human Immunodeficiency Virus and Hepatitis C Infection in South Dakota
Authors: Wesner Chelsea A , Zhang Weiwei , Melstad Sandra , Ruen Elizabeth , Deffenbaugh Cassandra , Gu Wei , Clayton Joshua L
Published: May 2020

Background

Key indicators of vulnerability for the syndemic of opioid overdose, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) due to injection drug use (IDU) in rural reservation and frontier counties are unknown. We examined county-level vulnerability for this syndemic in South Dakota.

Methods

Informed by prior methodology from the Centers for Disease Control and Prevention, we used acute and chronic HCV infections among persons aged ≤40 years as a proxy measure of IDU. Twenty-nine county-level indicators potentially associated with HCV infection rates were identified. Using these indicators, we examined relationships through bivariate and multivariate analysis and calculated a composite index score to identify the most vulnerable counties (top 20%) to this syndemic.

Results

Of the most vulnerable counties, 69% are reservation counties and 62% are rural. The county-level HCV infection rate is 4 times higher in minority counties than nonminority counties, and almost all significant indicators of opioid-related vulnerability in our analysis are structural and potentially modifiable through public health interventions and policies.

Conclusions

Our assessment gives context to the magnitude of this syndemic in rural reservation and frontier counties and should inform the strategic allocation of prevention and intervention services.
In vitro activity of sulbactam/durlobactam against global isolates of carbapenem-resistant Acinetobacter baumannii
Authors: Seifert Harald , Müller Carina , Stefanik Danuta , Higgins Paul G , Miller Alita , Kresken Michael
Published: May 2020

Objectives

To evaluate the activity of the novel broad-spectrum serine β-lactamase inhibitor durlobactam (ETX2514) combined with sulbactam against global isolates of carbapenem-resistant Acinetobacter baumannii with defined carbapenem resistance mechanisms compared with reference antimicrobials with known activity against Acinetobacter spp.

Methods

The susceptibility of 246 carbapenem-resistant non-duplicate A. baumannii isolates to sulbactam/durlobactam, amikacin, colistin, imipenem/sulbactam/durlobactam, imipenem, meropenem, minocycline and sulbactam was tested using broth microdilution. Isolates were obtained from various body sites from patients in 37 countries and from six world regions between 2012 and 2016. Identification of carbapenem resistance mechanisms and assignment to A. baumannii clonal lineages was based on WGS.

Results

Sulbactam/durlobactam showed excellent activity comparable to colistin but superior to amikacin, minocycline and sulbactam. The sulbactam/durlobactam MIC50/90 values were 1/4 and 2/4 mg/L and the colistin MIC50/90 values were 0.5 and 1 mg/L, respectively. Comparatively, amikacin, minocycline and sulbactam MIC50/90 values were 256/≥512, 2/16 and 16/64 mg/L, respectively.

Conclusions

Sulbactam/durlobactam had excellent in vitro potency against A. baumannii isolates, including those that were resistant to imipenem/meropenem, amikacin, minocycline and colistin, compared with other compounds. Sulbactam/durlobactam has the potential to become a useful addition to the limited armamentarium of drugs that can be used to treat this problem pathogen.
Patient safety and quality improvement: Ethical principles for a regulatory approach to bias in healthcare machine learning
Authors: McCradden Melissa D , Joshi Shalmali , Anderson James A , Mazwi Mjaye , Goldenberg Anna , Zlotnik Shaul Randi
Published: May 2020

Accumulating evidence demonstrates the impact of bias that reflects social inequality on the performance of machine learning (ML) models in health care. Given their intended placement within healthcare decision making more broadly, ML tools require attention to adequately quantify the impact of bias and reduce its potential to exacerbate inequalities. We suggest that taking a patient safety and quality improvement approach to bias can support the quantification of bias-related effects on ML. Drawing from the ethical principles underpinning these approaches, we argue that patient safety and quality improvement lenses support the quantification of relevant performance metrics, in order to minimize harm while promoting accountability, justice, and transparency. We identify specific methods for operationalizing these principles with the goal of attending to bias to support better decision making in light of controllable and uncontrollable factors.
Detection of Paralytic Shellfish Toxins in Southern Rock Lobster Jasus edwardsii Using the Qualitative Neogen™ Lateral Flow Immunoassay: Single-Laboratory Validation
Authors: Dorantes-Aranda Juan José , Hayashi Aiko , Turnbull Alison R , Jolley Jessica Y C , Harwood D Tim , Hallegraeff Gustaaf M
Published: May 2020

Background

Paralytic shellfish toxins (PST) are a significant problem for the Tasmanian shellfish and Southern Rock Lobster (Jasus edwardsii) industries, and the introduction of a rapid screening test in the monitoring program could save time and money.

Objective

The aim was to perform a single-laboratory validation of the Neogen rapid test for PST in the hepatopancreas of Southern Rock Lobster.

Methods

The AOAC INTERNATIONAL guidelines for the validation of qualitative binary chemistry methods were followed. Three different PST profiles (mixtures) were used, of which two were commonly found in naturally contaminated lobster hepatopancreas (high in gonyautoxin 2&3 and saxitoxin), and the third toxin profile was observed in a few select animals (high in gonyautoxin 1&4).

Results

The Neogen test consistently returned negative results for non-target toxins (selectivity). The probability of detection (POD) of PST in the lobster hepatopancreas using the Neogen test increased with increasing PST concentrations. POD values of 1.0 were obtained at ≥0.57 mg STX-diHCl eq/kg in mixtures 1 and 2, and 0.95 and 1.0 for mixture 3 at 0.79 and 1.21 mg STX-diHCl eq/kg, respectively, with a fitted POD of 0.98 for 0.80 mg STX-diHCl eq/kg. The performance of the Neogen test when using four different production lots (ruggedness) showed no significant differences.

Conclusions

The results of the validation study were satisfactory and the Neogen test is being trialed within the Tasmanian PST monitoring program of Southern Rock Lobster.

Highlights

The Neogen rapid kit was successfully validated for the detection of PST in Southern Rock Lobster hepatopancreas.
Site-specific epitope insertion into recombinant proteins using the MAP tag system
Authors: Wakasa Ayami , Kaneko Mika K , Kato Yukinari , Takagi Junichi , Arimori Takao
Published: May 2020

The MAP tag system comprises a 14-residue peptide derived from mouse podoplanin and its high-affinity monoclonal antibody PMab-1. We determined the crystal structure of PMab-1 complexed with the MAP tag peptide and found that the recognition required only the N-terminal 8 residues of MAP tag sequence, enabling the shortening of the tag length without losing the affinity for PMab-1. Furthermore, the structure illustrated that the MAP tag adopts a U-shaped conformation when bound by PMab-1, suggesting that loop-inserted MAP tag would assume conformation compatible with the PMab-1 binding. We inserted the 8-residue MAP tag into multiple loop regions in various proteins including fibronectin type III domain and G-protein-coupled receptors and tested if they maintain PMab-1 reactivity. Despite the conformational restraints forced by the insertion position, all MAP-inserted mutants were expressed well in mammalian cells at levels comparable to the non-tagged proteins. Furthermore, the binding by PMab-1 was fully maintained even for the mutant where MAP tag was inserted at a structurally restricted β-hairpin, indicating that the MAP tag system has unique feature that allows placement in the middle of protein domain at desired locations. Our results indicate the versatile utility of the MAP tag system in ‘site-specific epitope insertion’ application.
International Economic Law and Disintegration: Beware the Schmittean Moment
Authors: Arcuri Alessandra
Published: May 2020

In his influential book, Straight Talk on Trade, Dani Rodrik provides a cogent critique of the existing international economic order and concludes as follows: ‘So, I accept that nation-states are a source of disintegration for the global economy.’ This article critically engages with the idea that the nation-state is a legitimate force of disintegration of the international economic order, with particular attention to trade and investment agreements. In times of raising authoritarianism, it is crucial to reflect on some of the limits of the nation-state and on the necessity to develop alternative paradigms for integrating economies and societies. Against this background, this article posits that we should beware of the risk of a ‘Schmittean moment’. This term is used to refer to a major shift toward an ideal of unfettered national sovereignty as the chief paradigm to re-orient the international (economic) order. Under such ideal, any international normative benchmark is brushed away by an allegedly more intellectually honest ‘political’ dimension, which can find its realization only in the decisionist state. To understand the risk of a ‘Schmittean moment’ it is important to recognize that the move toward more nation-state is partly animated by some legitimate concerns over the existing international legal order, such as those underpinning the analysis by Dani Rodrik. This article articulates a two-fold critique of the idea that an expansion of national sovereignty is going to achieve a better socio-economic world order per se. The first critique is internal, showing that the nation-state does not possess intrinsic characteristics to facilitate democracy, equality, and sustainability. The second is external and focuses on the necessity to look reflexively at the goals of the system of international economic law, to re-imagine it as capable to address questions of inequality and environmental degradation.
The MUC6/AP2A2 Locus and Its Relevance to Alzheimer’s Disease: A Review
Authors: Nelson Peter T , Fardo David W , Katsumata Yuriko
Published: May 2020

We recently reported evidence of Alzheimer’s disease (AD)-linked genetic variation within the mucin 6 (MUC6) gene on chromosome 11p, nearby the adaptor-related protein complex 2 subunit alpha 2 (AP2A2) gene. This locus has interesting features related to human genomics and clinical research. MUC6 gene variants have been reported to potentially influence viral—including herpesvirus—immunity and the gut microbiome. Within the MUC6 gene is a unique variable number of tandem repeat (VNTR) region. We discovered an association between MUC6 VNTR repeat expansion and AD pathologic severity, particularly tau proteinopathy. Here, we review the relevant literature. The AD-linked VNTR polymorphism may also influence AP2A2 gene expression. AP2A2 encodes a polypeptide component of the adaptor protein complex, AP-2, which is involved in clathrin-coated vesicle function and was previously implicated in AD pathogenesis. To provide background information, we describe some key knowledge gaps in AD genetics research. The “missing/hidden heritability problem” of AD is highlighted. Extensive portions of the human genome, including the MUC6 VNTR, have not been thoroughly evaluated due to limitations of existing high-throughput sequencing technology. We present and discuss additional data, along with cautionary considerations, relevant to the hypothesis that MUC6 repeat expansion influences AD pathogenesis.
High proportion of asymptomatic and presymptomatic COVID-19 infections in air passengers to Brunei
Authors: Wong Justin , Abdul Aziz Anita B Z , Chaw Liling , Mahamud Abdirahman , Griffith Matthew M , Lo Ying-Ru , Naing Lin
Published: May 2020

We report early findings from COVID-19 cases in Brunei suggesting a remarkably high proportion of asymptomatic (12%) and presymptomatic (30%) cases. This proportion was even higher in imported cases. These have implications for measures to prevent onward local transmission and should prompt reconsideration of current testing protocols and safe de-escalation of social distancing measures.
Low temperature modulates natural peel degreening in lemon fruit independently of endogenous ethylene
Authors: Mitalo Oscar W , Otsuki Takumi , Okada Rui , Obitsu Saeka , Masuda Kanae , Hojo Yuko , Matsuura Takakazu , Mori Izumi C , Abe Daigo , Asiche William O , Akagi Takashi , Kubo Yasutaka , Ushijima Koichiro
Published: May 2020

Peel degreening is an important aspect of fruit ripening in many citrus fruit, and previous studies have shown that it can be advanced by ethylene treatment or by low-temperature storage. However, the important regulators and pathways involved in natural peel degreening remain largely unknown. To determine how natural peel degreening is regulated in lemon fruit (Citrus limon), we studied transcriptome and physiochemical changes in the flavedo in response to ethylene treatment and low temperatures. Treatment with ethylene induced rapid peel degreening, which was strongly inhibited by the ethylene antagonist, 1-methylcyclopropene (1-MCP). Compared with 25 ºC, moderately low storage temperatures of 5–20 °C also triggered peel degreening. Surprisingly, repeated 1-MCP treatments failed to inhibit the peel degreening induced by low temperature. Transcriptome analysis revealed that low temperature and ethylene independently regulated genes associated with chlorophyll degradation, carotenoid metabolism, photosystem proteins, phytohormone biosynthesis and signalling, and transcription factors. Peel degreening of fruit on trees occurred in association with drops in ambient temperature, and it coincided with the differential expression of low temperature-regulated genes. In contrast, genes that were uniquely regulated by ethylene showed no significant expression changes during on-tree peel degreening. Based on these findings, we hypothesize that low temperature plays a prominent role in regulating natural peel degreening independently of ethylene in citrus fruit.
The Impact of Military Pediatrics: Assessing Clinical, Leadership, Academic, and Operational Experience Among Pediatric-trained Graduates From the Uniformed Services University of the Health Sciences (USU)
Authors: Judd Courtney A , Dong Ting , Meyer Holly S , Hickey Patrick W , Torre Dario M , Durning Steven J
Published: May 2020

Introduction

This article uses alumni survey data from the Uniformed Services University of the Health Sciences (USU) F. Edward Hébert School of Medicine to assess the professional impact of pediatric-trained USU graduates over the course of their careers. We specifically report on the clinical and leadership roles held, career accomplishments, and operational involvement among military pediatricians.

Materials and Methods

This study analyzed survey data that were collected from alumni of USU. We used descriptive statistics to report the career achievements and operational experiences among USU graduates who completed training in pediatrics. This study was deemed exempt by the USU Institutional Review Board.

Results

The survey response rate was 49.5% among 2,400 eligible respondents. Out of 1,189 alumni respondents, 110 (9.3%) trained in pediatrics. Among the pediatric-trained USU graduates, 98.2% spent some time as a full-time clinician, 73.6% served as chief of a clinical service, 42.7% held the role of department chair/chief or the equivalent, and 26.3% filled leadership positions in deployed settings. Forty percent of USU-trained military pediatricians deployed to combat areas at least once, and 35.5% participated in at least one peacetime humanitarian mission.

Conclusions

Our findings contribute to the unique story of military pediatricians who graduated from USU. These uniformed pediatricians participate actively in all realms of military medicine and have demonstrated their versatility through participation in a wide variety of vital functions. Their contributions include the provision of clinical care for both military children and active duty service members, serving in varied leadership positions, engaging in health professions education and other academic pursuits, and participating in operational assignments. Future studies could aim to more fully address the diverse contributions of military pediatricians to the overall mission by including more specific data about career experiences from all uniformed pediatricians.
A missing outskirts problem? Comparisons between stellar haloes in the Dragonfly Nearby Galaxies Survey and the TNG100 simulation
Authors: Merritt Allison , Pillepich Annalisa , van Dokkum Pieter , Nelson Dylan , Hernquist Lars , Marinacci Federico , Vogelsberger Mark
Published: May 2020

Low surface brightness galactic stellar haloes provide a challenging but promising path towards unravelling the past assembly histories of individual galaxies. Here, we present detailed comparisons between the stellar haloes of Milky Way-mass disc galaxies observed as part of the Dragonfly Nearby Galaxies Survey (DNGS) and stellar mass-matched galaxies in the TNG100 run of the IllustrisTNG project. We produce stellar mass maps as well as mock g- and r-band images for randomly oriented simulated galaxies, convolving the latter with the Dragonfly point spread function (PSF) and taking care to match the background noise, surface brightness limits, and spatial resolution of DNGS. We measure azimuthally averaged stellar mass density and surface brightness profiles, and find that the DNGS galaxies generally have less stellar mass (or light) at large radii (>20 kpc) compared to their mass-matched TNG100 counterparts, and that simulated galaxies with similar surface density profiles tend to have low accreted mass fractions for their stellar mass. We explore potential solutions to this apparent ‘missing outskirts problem’ by implementing several ad hoc adjustments within TNG100 at the stellar particle level. Although we are unable to identify any single adjustment that fully reconciles the differences between the observed and simulated galaxy outskirts, we find that artificially delaying the disruption of satellite galaxies and reducing the spatial extent of in-situ stellar populations result in improved matches between the outer profile shapes and stellar halo masses, respectively. Further insight can be achieved with higher resolution simulations that are able to better resolve satellite accretion, and with larger samples of observed galaxies.
Searching for globular cluster chemical anomalies on the main sequence of a young massive cluster
Authors: Cabrera-Ziri I , Speagle J S , Dalessandro E , Usher C , Bastian N , Salaris M , Martocchia S , Kozhurina-Platais V , Niederhofer F , Lardo C , Larsen S S , Saracino S
Published: May 2020

The spectroscopic and photometric signals of the star-to-star abundance variations found in globular clusters seem to be correlated with global parameters like the cluster’s metallicity, mass, and age. Understanding this behaviour could bring us closer to the origin of these intriguing abundance spreads. In this work we use deep HST photometry to look for evidence of abundance variations in the main sequence of a young massive cluster NGC 419 (∼105 M⊙, ∼1.4 Gyr). Unlike previous studies, here we focus on stars in the same mass range found in old globulars (∼0.75–1 M⊙), where light elements variations are detected. We find no evidence for N abundance variations among these stars in the Un − B and U − B colour–magnitude diagrams of NGC 419. This is at odds with the N variations found in old globulars like 47 Tuc, NGC 6352, and NGC 6637 with similar metallicity to NGC 419. Although the signature of the abundance variations characteristic of old globulars appears to be significantly smaller or absent in this young cluster, we cannot conclude if this effect is mainly driven by its age or its mass.
A quasar microlensing light-curve generator for LSST
Authors: Neira Favio , Anguita Timo , Vernardos Georgios
Published: May 2020

We present a tool to generate mock quasar microlensing light curves and sample them according to any observing strategy. An updated treatment of the fixed and random velocity components of observer, lens, and source is used, together with a proper alignment with the external shear defining the magnification map caustic orientation. Our tool produces quantitative results on high magnification events and caustic crossings, which we use to study three lensed quasars known to display microlensing, viz. RX J1131–1231, HE 0230–2130, and Q 2237+0305, as they would be monitored by The Rubin Observatory Legacy Survey of Space and Time (LSST). We conclude that depending on the location on the sky, the lens and source redshift, and the caustic network density, the microlensing variability may deviate significantly than the expected ∼20-yr average time-scale (Mosquera & Kochanek 2011). We estimate that ∼300 high magnification events with Δmag>1 mag could potentially be observed by LSST each year. The duration of the majority of high magnification events is between 10 and 100 d, requiring a very high cadence to capture and resolve them. Uniform LSST observing strategies perform the best in recovering microlensing high magnification events. Our web tool can be extended to any instrument and observing strategy, and is freely available as a service at http://gerlumph.swin.edu.au/tools/lsst_generator/, along with all the related code.
First speckle interferometric measurements of binary stars at the Observatorio Astrofísico Guillermo Haro
Authors: Guerrero C A , Rosales-Ortega F F , Escobedo G , Martínez J , Castillo E , García-Flores P , Nieto-Suárez M A
Published: May 2020

In this paper, we present the first multiband speckle interferometric measurements of binary stars performed using the 2.1 m telescope of the Observatorio Astrofísico Guillermo Haro, Cananea, Sonora, México. We describe here FICCO: Fast Imaging Camera for Cananea Observatory, a new instrument developed to perform speckle observations from the Northern Hemisphere. We tested this new instrument with objects from the Washington Double Star Catalog, that were observed during three runs allocated in 2019. We report 480 astrometric measurements of 138 pairs, with angular separations ranging from 0.06 to 5.76 arcsec, including 347 measurements with separations smaller than 1 arcsec. We estimated a mean error in separation of 14 mas, 1.6° in position angle, and 0.45 mag for the magnitude difference. We confirmed 12 double stars discovered by Hipparcos. Finally, we present a correction to four previously published orbital solutions of visual binaries.