bluuebunny/crossref_metadata_2025 huggingface dataset:
Disclosing the Molecular Mechanism of Iron Incorporation in Listeria innocua Dps by EPR Spectroscopy
Authors: Ilari Andrea , Bellapadrona Giuliano , Carbonera Donatella , Di Valentin Marilena
Published: November 2020

Bacteria overexpress, under condition of starvation or oxidative stress, Dps (DNA-binding proteins from starved cells), hollow sphere formed by 12 identical subunits endowed with ferritin-like activity. The iron oxidation and incorporation in Dps take place using H2O2 produced under starvation as preferred iron oxidant, thereby protecting bacteria from oxidative damage. Even if the role of Dps is well known, the mechanism of iron oxidation and incorporation remain to be elucidated. Here, we have used the EPR technique to shed light on the Fe(II) binding and oxidation mechanism at the ferroxidase center using both the wild-type (wt) protein and mutants of the iron ligands (H31G, H43G and H31G-H43G-D58A). The EPR titration of wt Dps and the H31G mutant with Fe(II) upon H2O2 addition shows that Fe(II) is oxidized with the increase of the signal at g = 4.3, reaching a maximum for 12 Fe(II)/subunit. The EPR signal becomes negligible when the titration is carried out on the triple mutant. These experiments indicate that the iron firstly occupied the A site at the ferroxidase center and confirm that the residues H31, H43 and D58 have a key role in the iron oxidation and incorporation process. Moreover, the data indicate that the ferroxidase center, upon mutation of H31 or H43 to Gly, changes the mode of iron binding. Finally, we demonstrate here that, when the iron micelle forms, the EPR signal at g = 4.3 disappears indicating that iron leaves the ferroxidase center to reach the inner cavity.
Health care consumption and psychiatric diagnoses among adolescent girls 1 and 2 years after a first-time registered child sexual abuse experience: a cohort study in the Stockholm Region
Authors: Rajan Gita , Syding Sanna , Ljunggren Gunnar , Wändell Per , Wahlström Lars , Philips Björn , Svedin Carl Göran , Carlsson Axel C.
Published: November 2020

Child sexual abuse (CSA) is a crime against human rights with severe health consequences, and suicidal actions, stress, eating disorders, and borderline disorder are common among survivors of CSA. The objective of this study was to analyze how health care consumption patterns developed among adolescent girls in the Stockholm Region, Sweden, 1 and 2 years after the first registration of CSA experience appeared in their medical record, as compared to age-matched controls without such registration. In this cohort study, number of healthcare visits, comorbidities, and prescribed drugs were collected through the Stockholm Region administrative database (VAL), for girls age 12–17 with registration of CSA experience in their medical record (n = 519) and age-matched controls (n = 4920) between 2011 and 2018. Healthcare consumption patterns remained higher among the girls with a registered CSA experience compared to the controls, both 1 and 2 years after the first CSA experience registration. Highest odds ratios (ORs) were found for suicide attempts [OR 26.38 (12.65–55.02) and 6.93 (3.48–13.49)]; stress disorders [25.97 (17.42–38.69) and 15.63 (9.82–24.88)]; psychosis [OR 19.39 (1.75–214.13) and 9.70 (1.36–68.95)], and alcohol abuse [OR 10.32 (6.48–16.44) and 6.09 (1.98–18.67)], 1 and 2 years, respectively, after the first CSA experience registration. The drug prescriptions were also significantly higher among the girls with a CSA experience registration than for the controls. The results highlight the need to systematically evaluate and develop assessment, treatment planning, and interventions offered to adolescent girls after their first CSA experience registration.
Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship
Authors: Rothe Kathrin , Feihl Susanne , Schneider Jochen , Wallnöfer Fabian , Wurst Milena , Lukas Marina , Treiber Matthias , Lahmer Tobias , Heim Markus , Dommasch Michael , Waschulzik Birgit , Zink Alexander , Querbach Christiane , Busch Dirk H. , Schmid Roland M. , Schneider Gerhard , Spinner Christoph D.
Published: November 2020

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17–99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1–13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.
Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial
Authors: Fujitani Kazumasa , Shitara Kohei , Takashima Atsuo , Koeda Keisuke , Hara Hiroki , Nakayama Norisuke , Hironaka Shuichi , Nishikawa Kazuhiro , Kimura Yutaka , Amagai Kenji , Hosaka Hisashi , Komatsu Yoshito , Shimada Ken , Kawabata Ryohei , Ohdan Hideki , Kodera Yasuhiro , Nakamura Masato , Nakajima Takako Eguchi , Miyata Yoshinori , Moriwaki Toshikazu , Kusumoto Tetsuya , Nishikawa Kazuo , Ogata Kazuhiro , Shimura Masashi , Morita Satoshi , Koizumi Wasaburo
Published: November 2020

Background

This study evaluated the association between early tumor response at 8 weeks, previously reported as a positive outcome prognosticator, and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients enrolled in the ABSOLUTE trial.

Methods

HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D) utility index score in patients with complete response (CR) + partial response (PR) and progressive disease (PD) at 8 weeks, and time-to-deterioration (TtD) of the EQ-5D score, with the preset minimally important difference (MID) of 0.05, was compared between these populations. Among the enrolled patients, 143 and 160 patients were assessable in weekly solvent-based paclitaxel (Sb-PTX) arm and weekly nanoparticle albumin-bound paclitaxel (nab-PTX) arm, respectively.

Results

Changes of the EQ-5D score from baseline to 8 weeks in the nab-PTX arm were 0.0009 and − 0.1229 in CR + PR and PD patients, respectively; the corresponding values for the Sb-PTX arm were − 0.0019 and − 0.1549. For both treatments, changes of the EQ-5D score from baseline at 8 weeks were significantly larger in patients with PD than in those with CR + PR. The median TtD was 3.9 and 2.2 months in patients with CR + PR and PD, respectively, for nab-PTX [hazard ratio (HR) = 0.595, 95% confidence interval (CI) 0.358–0.989]. For Sb-PTX, the corresponding values were 4.7 and 2.0 months (HR = 0.494, 95% CI 0.291–0.841).

Conclusions

Early tumor shrinkage was associated with maintained HRQOL in AGC patients on the second-line chemotherapy with taxanes.
A protocol for monitoring plant responses to changing nitrogen deposition regimes in Alberta bogs
Authors: Vitt Dale H. , House Melissa , Kitchen Samantha , Wieder R. Kelman
Published: November 2020

Bogs are nutrient poor, acidic ecosystems that receive their water and nutrients entirely from precipitation (= ombrogenous) and as a result are sensitive to nutrient loading from atmospheric sources. Bogs occur frequently on the northern Alberta landscape, estimated to cover 6% of the Athabasca Oil Sands Area. As a result of oil sand extraction and processing, emissions of nitrogen (N) and sulfur (S) to the atmosphere have led to increasing N and S deposition that have the potential to alter the structure and function of these traditionally nutrient-poor ecosystems. At present, no detailed protocol is available for monitoring potential change of these sensitive ecosystems. We propose a user-friendly protocol that will monitor potential plant and lichen responses to future environmental inputs of nutrients and provide a structured means for collecting annual data. The protocol centers on measurement of five key plant/lichen attributes, including changes in (1) plant abundances, (2) dominant shrub annual growth and primary production, (3) lichen health estimated through chlorophyll/phaeophytin concentrations, (4) Sphagnum annual growth and production, and (5) annual growth of the dominant tree species (Picea mariana). We placed five permanent plots in each of six bogs located at different distances from the center of oil sand extraction and sampled these for 2 years (2018 and 2019). We compared line intercept with point intercept plant assessments using NMDS ordination, concluding that both methods provide comparable data. These data indicated that each of our six bog sites differ in key species abundances. Structural differences were apparent for the six sites between years. These differences were mostly driven by changes in Vaccinium oxycoccos, not the dominant shrubs. We developed allometric growth equations for the dominant two shrubs (Rhododendron groenlandicum and Chamaedaphne calyculata). Equations developed for each of the six sites produced growth values that were not different from one another nor from one developed using data from all sites. Annual growth of R. groenlandicum differed between sites, but not years, whereas growth of C. calyculata differed between the 2 years with more growth in 2018 compared with 2019. In comparison, Sphagnum plant density and stem bulk density both had strong site differences, with stem mass density higher in 2019. When combined, annual production of S. fuscum was greater in 2019 at three sites and not different at three of the sites. Chlorophyll and phaeophytin concentrations from the epiphytic lichen Evernia mesomorpha also differed between sites and years. This protocol for field assessments of five key plant/lichen response variables indicated that both site and year are factors that must be accounted for in future assessments. A portion of the site variation was related to patterns of N and S deposition.
The influence of land abandonment on forest disturbance regimes: a global review
Authors: Mantero Giulia , Morresi Donato , Marzano Raffaella , Motta Renzo , Mladenoff David J. , Garbarino Matteo
Published: November 2020

Context

Since the nineteenth century, rural areas have experienced progressive abandonment mostly due to socioeconomic changes, with direct and indirect effects on forest disturbance regimes occurring in these human-dominated landscapes. The role of land abandonment in modifying disturbance regimes has been highlighted for some types of disturbances, albeit being still somewhat overlooked compared to climate change.

Objectives

This literature review is aimed at highlighting the most relevant effects of land abandonment and land-use legacy on the regime of different types of forest disturbances, providing insight into land-use change/disturbances interactions.

Methods

We searched in the Scopus and Web of Science databases for relevant studies at the global scale dealing with eight major natural disturbances: avalanche, flooding, herbivory, insect outbreak, landslide, rockfall, wildfire and windthrow. We classified papers into five relevance classes, with the highest score (4) assigned to studies quantitatively measuring the interactions between abandonment dynamics and disturbance regimes.

Results

Most papers focused on wildfires in Mediterranean Europe in the twentieth century, where landscape homogenisation and fuel build-up contributed to worsening their frequency, size and severity. Dense forests developed following land abandonment instead exert inhibiting effects toward mass movements such as avalanches, rockfalls and landslides. Regarding the other investigated disturbances, we found only a few studies presenting site-specific and partly contrasting effects.

Conclusions

Land abandonment triggers ecological processes at the landscape scale, altering land cover patterns and vegetation communities, which in turn affect disturbance regimes. Implications for land and resource management mostly depend on the stage at which post-abandonment secondary succession has developed.
Illuminating single genomic loci in live cells by reducing nuclear background fluorescence
Authors: Lu Song , Wang Dianbing , Hou Yu , Guo Dongge , Deng Yulin , Zhang Xian-En
Published: November 2020

The tagging of genomic loci in living cells provides visual evidence for the study of genomic spatial organization and gene interaction. CRISPR/dCas9 (clustered regularly interspaced short palindromic repeats/deactivated Cas9) labeling system labels genes through binding of the dCas9/sgRNA/fluorescent protein complex to repeat sequences in the target genomic loci. However, the existence of numerous fluorescent proteins in the nucleus usually causes a high background fluorescent readout. This study aims to limit the number of fluorescent modules entering the nucleus by redesigning the current CRISPR/dCas9-SunTag labeling system consisting of dCas9-SunTag-NLS (target module) and scFv-sfGFP-NLS (signal module). We removed the nuclear location sequence (NLS) of the signal module and inserted two copies of EGFP into the signal module. The ratio of the fluorescent intensity of the nucleus to that of the cytoplasm (N/C ratio) was decreased by 71%, and the ratio of the signal to the background (S/B ratio) was increased by 1.6 times. The system can stably label randomly selected genomic loci with as few as 9 repeat sequences.
Induction of Noonan syndrome-specific human-induced pluripotent stem cells under serum-, feeder-, and integration-free conditions
Authors: Hamada Atsuko , Akagi Eri , Obayashi Fumitaka , Yamasaki Sachiko , Koizumi Koichi , Ohtaka Manami , Nishimura Ken , Nakanishi Mahito , Toratani Shigeaki , Okamoto Tetsuji
Published: November 2020

Noonan syndrome is an autosomal dominant developmental disorder. Although it is relatively common, and its phenotypical variability is well documented, its pathophysiology is not fully understood. Previously, with the aim of revealing the pathogenesis of genetic disorders, we reported the induction of cleidocranial dysplasia-specific human-induced pluripotent stem cells (hiPSCs) from patient’s dental pulp cells (DPCs) under serum-free, feeder-free, and integration-free conditions. Notably, these cells showed potential for application to genetic disorder disease models. Furthermore, using similar procedures, we reported the induction of hiPSCs derived from peripheral blood mononuclear cells (PBMCs) of healthy volunteers. These methods are beneficial, because they are carried out without invasive and painful biopsies. Using those procedures, we reprogrammed DPCs and PBMCs that were derived from a patient with Noonan syndrome (NS) to establish NS-specific hiPSCs (NS-DPC-hiPSCs and NS-PBMC-hiPSCs, respectively). The induction efficiency of NS-hiPSCs was higher than that of WT-hiPSCs. We hypothesize that this was caused by high NANOG expression. Here, we describe the experimental results and findings related to NS-hiPSCs. This is the first report on the establishment of NS-hiPSCs and their disease modeling.
Effectiveness of a Low-Calorie Diet for Liver Volume Reduction Prior to Bariatric Surgery: a Systematic Review
Authors: Romeijn Marleen M. , Kolen Aniek M. , Holthuijsen Daniëlle D. B. , Janssen Loes , Schep Goof , Leclercq Wouter K. G. , van Dielen François M. H.
Published: November 2020

An energy-restricted diet is often prescribed before bariatric surgery to reduce weight and liver volume. While very-low-calorie diets (VLCDs, 450–800 kcal per day) have shown to be effective, the effectiveness of low-calorie diets (LCDs, 800–1500 kcal per day) is less obvious. The objective of this systematic review was to elucidate the effectiveness of LCD on liver volume reduction in patients awaiting bariatric surgery. Eight studies (n = 251) were included describing nine different diets (800–1200 kcal, 2–8 weeks). An LCD was effective in liver volume reduction (12–27%) and weight loss (4–17%), particularly during the first weeks. The LCD showed an acceptable patients’ compliance. Based on these findings, an LCD (800–1200 kcal), instead of a VLCD, for 2 to 4 weeks should be preferred.
Justifying Limitations on the Freedom of Expression
Authors: Gunatilleke Gehan
Published: November 2020

The freedom of expression is vital to our ability to convey opinions, convictions, and beliefs, and to meaningfully participate in democracy. The state may, however, ‘limit’ the freedom of expression on certain grounds, such as national security, public order, public health, and public morals. Examples from around the world show that the freedom of individuals to express their opinions, convictions, and beliefs is often imperilled when states are not required to meet a substantial justificatory burden when limiting such freedom. This article critiques one of the common justificatory approaches employed in a number of jurisdictions to frame the state’s burden to justify limitations on the freedom of expression—the proportionality test. It presents a case for an alternative approach that builds on the merits and addresses some of the weaknesses of a typical proportionality test. This alternative may be called a ‘duty-based’ justificatory approach because it requires the state to demonstrate—through the presentation of publicly justifiable reasons—that the individual concerned owes others a duty of justice to refrain from the expressive conduct in question. The article explains how this approach is more normatively compelling than a typical proportionality test. It also illustrates how such an approach can better constrain the state’s ability to advance majoritarian interests or offload its positive obligations by limiting the freedom of expression of minorities and dissenting voices.
The role of hepatobiliary scintigraphy combined with spect/ct in predicting severity of liver failure before major hepatectomy: a single-center pilot study
Authors: Serenari Matteo , Bonatti Chiara , Zanoni Lucia , Peta Giuliano , Tabacchi Elena , Cucchetti Alessandro , Ravaioli Matteo , Pettinato Cinzia , Bagni Alberto , Siniscalchi Antonio , D’Errico Antonietta , Golfieri Rita , Fanti Stefano , Cescon Matteo
Published: November 2020

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the “50–50 criteria” PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient’s clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the “50–50 criteria”, ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.
Drought responses and their effects on radial stem growth of two co-occurring conifer species in the Mediterranean mountain range
Authors: Güney Aylin , Zweifel Roman , Türkan Semra , Zimmermann Reiner , Wachendorf Magnus , Güney Coşkun Okan
Published: November 2020

Key message

Patterns of stem radial variations showed thatCedrus libaniA. Rich. was less limited by summer drought than co-occurringJuniperus excelsaM. Bieb.Cedrus libanirecovered faster from tree water deficit and showed significantly higher radial growth rates and annual stem increments thanJ. excelsa. However, the ability ofJ. excelsato grow more hours per year may indicate a potential benefit in more extreme conditions.

Context

Knowledge about species-specific drought responses is needed to manage productive forests in drought prone areas. Under water shortage, trees commonly show stem shrinkage, which is assumed to inhibit growth.

Aims

We investigated whether the two co-existing conifers Juniperus excelsa M. Bieb. and Cedrus libani A. Rich. (growing at the Taurus Mountains, SW-Turkey) show differences in water relations and stem growth in order to evaluate their respective drought tolerance.

Methods

Stem radius changes were hourly monitored over 2 years using high-resolution point dendrometers. Radial stem growth, tree water deficit-induced stem shrinkage, and maximum daily shrinkage were extracted from stem radius change measurements, investigated for their patterns, and related to environmental conditions.

Results

Cedrus libani recovered from tree water deficit under higher temperature and vapor pressure deficit than J. excelsa. The number of hours during which stem growth occurred was higher for J. excelsa; however, growth rates and annual increments were significantly lower than in C. libani. Both species showed highest maximum daily shrinkage during the driest months indicating the ability to maintain gas exchange all year round.

Conclusion

Juniperus excelsa showed a more conservative growth strategy while C. libani was less limited by summer drought and showed more annual stem increment under the conditions investigated.
Corrosion Inhibition of Mild Steel in Acidic Media by N-[(3,4-Dimethoxyphenyl)Methyleneamino]-4-Hydroxy-Benzamide
Authors: Muthamma Kashmitha , Kumari Preethi , Lavanya M. , Rao Suma A.
Published: November 2020

Mild steel (a low carbon steel) is an affordable engineering material used for many purposes in various environments including mild acidic environment with some precautions. The corrosion behaviour of mild steel (MS) in 0.5 M H2SO4and 0.5 M HCl, in the temperature range (303–323 K) without and with the inhibitorN-[(3,4-dimethoxyphenyl) methyleneamino]-4-hydroxy-benzamide (DMHB), was investigated using Potentiodynamic polarization and Electrochemical impedance spectroscopy (EIS) techniques supplementing with surface characterization study using scanning electron microscope (SEM) and atomic force spectroscopy (AFM). Experimental observations were found to be in agreement with Density functional theory (DFT) calculations. The inhibition efficiency increases with increase in DMHB concentration and showed maximum inhibition efficiency of 86% in 0.5 M H2SO4and 81% in 0.5 M HCl, respectively, at concentration of 3 × 10─3 M at 303 K. The inhibition efficiency of DMHB obtained relatively at its lower concentration (3 × 10─3 M) compared to other reported related compounds confirms its potential towards corrosion inhibition. The variation in the kinetic and thermodynamic parameters indicated physisorption of DMHB on MS and its mixed type inhibitive action followed Langmuir’s isotherm model. DFT calculations go along with the experimental results, signifying the potential corrosion inhibition behaviour of DMHB for MS in both the acid media.
A computational intelligence enabled honeypot for chasing ghosts in the wires
Authors: Naik Nitin , Jenkins Paul , Savage Nick , Yang Longzhi
Published: November 2020

A honeypot is a concealed security system that functions as a decoy to entice cyberattackers to reveal their information. Therefore, it is essential to disguise its identity to ensure its successful operation. Nonetheless, cyberattackers frequently attempt to uncover these honeypots; one of the most effective techniques for revealing their identity is a fingerprinting attack. Once identified, a honeypot can be exploited as a zombie by an attacker to attack others. Several effective techniques are available to prevent a fingerprinting attack, however, that would be contrary to the purpose of a honeypot, which is designed to interact with attackers to attempt to discover information relating to them. A technique to discover any attempted fingerprinting attack is highly desirable, for honeypots, while interacting with cyberattackers. Unfortunately, no specific method is available to detect and predict an attempted fingerprinting attack in real-time due to the difficulty of isolating it from other attacks. This paper presents a computational intelligence enabled honeypot that is capable of discovering and predicting an attempted fingerprinting attack by using a Principal components analysis and Fuzzy inference system. This proposed system is successfully tested against the five popular fingerprinting tools Nmap, Xprobe2, NetScanTools Pro, SinFP3 and Nessus.
Multilayer network analysis of the drugs development cycle in the global pharmaceutical industry
Authors: Goto Hiromitsu , Jibu Mari , Souma Wataru , Ikeda Yuichi
Published: November 2020

Drug development is a time-consuming process from the start of research to obtaining approval, and the probability of success with a candidate compound is extremely low. We aim to understand the characteristics of the flow and localization of knowledge during drug development in the global pharmaceutical industry. We analyze the multilayer network constructed with the drug pipeline layer, global supply chain layer, and global ownership layer. First, we identify the bow-tie structure and the community structure of each network layer. The obtained bow-tie structure shows the large strongly connected component and suggests that the knowledge flow in drug pipelines has similar characteristics as the supply chain network. The communities in each layer are characterized by country, category of the company, and bow tie component. We then study the multilayer network’s knowledge flow, conduct a statistical test, and verify the significance of the overlapping links between the drug pipeline and supply chain layers. Our results suggest a strong connection between open innovation in the pharmaceutical industry and firms’ economic activities in the supply chain.
The Boundaries of the EU Internal Market
Authors: Öberg Marja-Liisa
Published: November 2020

The book examines the twofold 'boundaries' of the concept of the European Union's internal market – the geographical and the substantive – through the prism of expanding the internal market to third countries without enlarging the Union. The book offers a comprehensive analysis of the conditions under which the internal market can effectively be extended to third countries by exporting EU acquis via international agreements without sacrificing its defining characteristics. Theoretical rather than empirical in approach, the book scrutinises and meticulously questions the required level of uniformity within flexible integration relating to the substantive scope of the internal market, the role of foundational principles in the European Union's market edifice, and the institutional framework necessary for granting third country actors full participation in the internal market while safeguarding the autonomy of the Union's legal order.
Anatomy of Flowering Plants
Authors: Rudall Paula J.
Published: November 2020

Understanding plant anatomy is not only fundamental to the study of plant systematics and palaeobotany, but is also an essential part of evolutionary biology, physiology, ecology and the rapidly expanding science of developmental genetics. This modernised new edition covers all aspects of comparative plant structure and development, arranged in a series of chapters on the stem, root, leaf, flower, pollen, seed and fruit. Internal structures are described using magnification aids from the simple hand-lens to the electron microscope. Numerous references to recent topical literature are included, and new illustrations reflect a wide range of flowering plant species. The phylogenetic context of plant names has been updated as a result of improved understanding of the relationships among flowering plants. This clearly written text is ideal for students studying a wide range of courses in botany and plant science, and is also an excellent resource for professional and amateur horticulturists.
Creation and purpose: A conversation on art created by students at the Shingwauk Residential School
Authors: Hogan Skylee-Storm , McCracken Krista
Published: November 2020

What are the ethics behind caring, preserving, and displaying artwork created by Residential School Survivors? By looking at sketches and small handicrafts held by the Shingwauk Residential Schools Centre this piece examines the possibilities for caring for this unique type of Indigenous artwork in a culturally appropriate and ethical manner.
Risk Factors and Mortality in Pediatric Patients with Stenotrophomonas maltophilia Bacteremia
Authors: Alsuhaibani Mohammed , Aljarboua Alanoud , Althawadi Sahar , Alsweed Abdurahman , Al-Hajjar Sami
Published: November 2020

Background:Stenotrophomonas maltophilia (S. maltophilia) is an opportunistic and nosocomial pathogen that can cause an invasive and fatal infection, particularly in hospitalized and immunocompromised patients. However, little is known about the impact of S. maltophilia bacteremia in pediatric patients. Therefore, we aimed to identify risk factors for mortality, antibiotic susceptibility of S. maltophilia, and mortality rates in pediatric patients with S. maltophilia bacteremia. Methods: We conducted a retrospective cohort study by identifying all S. maltophilia–positive blood cultures in the microbiology laboratory database between January 2007 and December 2018 from hospitalized pediatric patients (age, 1–14 years) at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. After identifying patients with S. maltophilia bacteremia, medical charts were reviewed for demographics, clinical data, and outcome within 7 days of bacteremia diagnosis. Risk factors associated with mortality in S. maltophilia bacteremia patients were determined using univariate and multivariate analyses. Results: Overall, 68% of pediatric patients with S. maltophilia bacteremia were identified. The most common underlying primary diagnoses were malignancy (29.4%), congenital heart diseases (16.2%), anemia (14.7%), and primary immunodeficiency (11.8%). All infections were nosocomial infections, and (88.2%) bacteremia cases were central-line–associated bloodstream infections. The risk factors associated with mortality as determined by univariate analysis were ICU admission (P < .001), intubation (P = .001), neutropenia (P = .008), prior use of carbapenem (P = .002), thrombocytopenia (P = .006), and respiratory colonization (P < .001). On multivariate analysis, ICU admission (P = .007; 95% CI, 0.003–0.406) and neutropenia (P = .009; 95% CI, 0.013–0.537) were the major risk factors associated with mortality. S. maltophilia was the most susceptible to trimethoprim and sulfamethoxazole (TMP/SMX, 94.1%), followed by levofloxacin (85.7%). In addition, 36 patients received TMP/SMX as monotherapy, and 11 patients received it in combination with other antibiotics (fluoroquinolone, ceftazidime, or aminoglycoside). Hence, no statistically significant difference was observed in patient mortality. The overall mortality rate within 7 days of S. maltophilia bacteremia diagnosis was 33.8%. Conclusions:S. maltophilia bacteremia is a devastating emerging infection associated with high mortality among hospitalized children. Therefore, early diagnosis and prompt management based on local susceptibility data are crucial. Various risk factors, especially ICU admission and neutropenia, are associated with S. maltophilia bacteremia mortality.

Funding: None

Disclosures: None
Save Carbapenem Campaign: Assessment of Antibiotic Combinations Against Multidrug-Resistant Gram-Negative Bacilli
Authors: Tellis Rouchelle , Ignatius Anand
Published: November 2020

Background: Infections caused by multidrug-resistant gram-negative bacilli (MDR GNB) are a therapeutic challenge to clinicians. Combination antimicrobial therapy with empirically selected antibiotics is often used to treat these infections. This approach is ill advised because the antibiotics selected may not be optimal because of different killing activity. We aimed to determine the in vitro efficacy of antibiotic combinations devoid of carbapenems to explore potential synergy between antibiotics of different chemical classes. Methods: Prospective, experimental descriptive study of 85 MDR GNB isolated from clinical samples. The minimum inhibitory concentrations (MICs) of ceftazidime, amikacin, imipenem, and ciprofloxacin were determined by broth microdilution. The in-vitro effects of CAZ–AMK, CAZ–CIPRO, IMP–AMK and IMP–CIPRO combinations were studied by checker-board assay. Results: ESBL, AmpC, and MBL production was observed among 62.35%, 27.05%, and 44.70% of the MDR GNB, respectively. Moreover, 27.05% coproduced multiple β-lactamases. The MIC90 ranges were 16 to ≥1028 μg/mL for CAZ; 0.25 to ≥256 μg/mL for Amk, 0.25 to 12 μg/mL for CIPRO; and 0.125 to 512 μg/mL for IMP. CAZ–AMK and IMP–AMK combinations showed synergistic effects in >85% of MDR-GNB, with a fractional inhibitory concentration index ≤0.5. Higher rates of indifference and antagonism were observed with combinations including fluroquinolones. Conclusions: The in vitro antimicrobial activity of antibiotic combinations having third- or fourth-generation cephalosporin with aminoglycosides was comparable to that of imipenem alone or in combination therapy. Combinations devoid of carbapenems should be advocated to prolong the clinical usefulness of this antibiotic group

Funding: None

Disclosures: None
Semiquantitative Staphylococcus aureus Nasal Colony Reduction in Elective Orthopedic Surgery Reduces Surgical Site Infection
Authors: Saidel Lisa , Yosipovich Riki , Nativ Ronit , Sagi Orli , Shimoni Orly , Borer Abraham
Published: November 2020

Background: Clean surgical procedures such as hip and knee replacement and spine surgery have a low infection complication rate; however, if infections occur, there is substantial morbidity and increased cost. Staphylococcus aureus causes 30% of surgical site infections (SSIs). S. aureus colonization increases the risk of developing SSI. Nasal povidone-iodine 5% application reduces the S. aureus colonization burden. Objective: We aimed to reduce SSIs by applying nasal povidone-iodine 5% prior to hip and knee replacement and spine surgery. Methods: Adult patients hospitalized for elective hip replacement, knee replacement, or spine surgeries from February 2018 through August 2019 comprised the study cohort. All patients received preoperative guidance in the outpatient clinic. On admission, the evening before surgery, a nasal swab for S. aureus colonization was performed, followed by povidone-iodine 5% application in both nostrils and body chlorhexidine gluconate 4% bathing. Application of these substances was repeated in the morning before surgery. Within 24 hours after surgery, an additional nasal swab for S. aureus colonization was taken. A 90-day follow-up for SSI was done. Data were compared with a similar 2016–2017 cohort without the preoperative measures. Results: In total, 186 patients were included: 85 underwent hip or knee replacement (age 69 ± 13.2 y, 66% men), and 101 spine surgery (age 55 ± 15.4 y, 52% men). At screening, 18.3% were colonized with methicillin-sensitive S. aureus and 1.6% colonized with methicillin-resistant S. aureus. Pre- and postsurgery data for the cohort appear in Table 1. The SSI rate per 100 patient days for hip and knee replacement and for spine surgery decreased from 0.29 and 4.0, respectively, in the 2016–2017 cohort to 0 and 0.99, respectively, in the present cohort. Conclusions: Nasal povidone-iodine 5% reduced the S. aureus colonization burden. The SSI rate in elective hip and knee replacement and spine surgery significantly decreased. We show that there is no need for S. aureus eradication presurgery; semiquantitative S. aureus nasal colony reduction should suffice in reducing SSIs. Further research is needed using quantitative measurements for S. aureus colonization.

Funding: None

Disclosures: None
Seroprevalence of Mumps in Healthcare Workers in South Korea
Authors: Kim Sun Kyung , Jung Jiwon , Kwak Sun Hee , Hong Min Jee , Kim Eun Ok , Kim Sung-Han
Published: November 2020

Background: Mumps, a contagious disease, is transmissible by respiratory droplet particles and is preventable by vaccination. In South Korea, mandatory vaccination against mumps has markedly reduced its incidence. However, both the incidence and the number of reported cases of mumps have persistently increased in South Korea since 2007. Despite high vaccination rates, mumps outbreaks continue to occur, and many studies have been conducted on mumps seroprevalence in children and adolescents. In comparison, few reports have been published regarding mumps seroprevalence in healthcare workers (HCWs) in South Korea. Objective: We investigated the seroprevalence of HCWs in South Korea. Methods: This study was conducted at Asan Medical Center, a 2,705-bed tertiary-care hospital in Seoul, South Korea, with 8,329 HCWs. In 2018, we performed mumps antibody testing for HCWs. We administered MMR vaccination to all HCWs whose antibody test yielded equivocal or negative results. However, we did not repeat mumps antibody testing after MMR vaccination. Results: In total, 6,055 HCWs (73%) underwent mumps antibody testing. The overall mumps seropositivity rate was 87% (95% CI, 86%–87%). Seropositivity rates of all birth cohorts ranged from 72% to 92%. Mumps seropositivity rates were 88% in HCWs born before 1970, 87% in those born between 1970 and 1989, and 88% in those born between 1990 and 1995 (P = .59). Mumps seropositivity rates for both women and men HCWs were 87% (3,770 of 4,311 women and 1,517 of 1,744 men); the difference was not statistically significant (P = .62). The overall mumps seropositivity rate was 87%, which was above the herd immunity threshold of 75%–86%. Conclusions: Our results revealed that the overall mumps seropositivity rate in South Korean HCWs was above the herd immunity threshold. On the basis of this finding, we recommend that MMR vaccination after serologic testing may be a more reasonable approach than universal MMR vaccination alone in Korea.

Funding: None

Disclosures: None
Sherlock Holmes: Whose Tissue Is It Anyway?
Authors: Lee Bonita , Silverman Jason , Lacson Atilano , Izevbaye Iyare , Huynh Hien , Sergi Consolato , Maglantay Remegio , Mather Cheryl , Box Adrian , Paonessa Teresa , Nawaz Rebecca , Pulongbarit Jesusa , Tremblay Mario , VanVeen Kathy , Durand Joan , Cordoviz Melody , Aelick Nancy , Williamson Catherine
Published: November 2020

Background: The medical device reprocessing department (MDRD) is a crucial patient safety area with checkpoints to ensure appropriate reprocessing. Objective: We report the application of molecular pathology in the investigation of potential blood and body fluid exposure (BBFE) during endoscopy. Methods: When there is a potential BBFE from a medical device, our hospital has a systematic process whereby the clinical area involves the MDRD and the infection prevention control (IPC) team. The MDRD provides reprocessing documentation, including detailed information regarding the prior use of the devices. The clinician and the IPC physician discuss the risk of BBFE. If patient disclosure occurs, the IPC physician provides follow-up as appropriate. This report illustrates the collaboration of clinicians, the IPC team, the MDRD, pathologists, and molecular pathologists in investigating the possibility of residual human tissue and BBFE during endoscopy. Case reports: Two independent but similar events occurred in September 2016 and September 2019 in the pediatric endoscopy suite at our site, a tertiary-care pediatric hospital with 163 beds in Edmonton, Canada. During both endoscopies, the pediatric gastroenterologists observed a piece of tissue ejected from the gastroscope into the intestinal lumen when the biopsy forceps were pushed out of the channel for the first time. This observation raised concerns of possible gaps in the reprocessing of the endoscope and residual tissue remaining in the working channel after its last use. Both gastroenterologists were able to retrieve the presumed foreign tissue; however, both patients had possible BBFE because the mucosal surface was breached by the biopsy forceps. The MDRD reprocessing of both endoscopes was reviewed, and no gap was identified. In discussion with the pathologists and molecular pathologists, human identity testing using genetic markers was performed on the biopsy blocks of the previous patient on whom the endoscope was used, the potentially exposed patient, and the presumed foreign tissue for each event. The test results indicated that the presumed foreign tissue was in fact from the potentially exposed patient and therefore there was no BBFE. It is presumed that the working channel itself captured a small amount of the patient’s tissue during scope insertion. The results were a relief to the patients and families. Conclusions: It is prudent to investigate residual foreign tissue in a medical device that is being used on patients with mucosal breaches. Molecular pathology involving human identity testing is a very useful tool in the investigation of these types of events.

Funding: None

Disclosures: None
STOP-BSI: Reducing Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Oncology Patients
Authors: Yun Mylinh , Varkey Jay , Spinke Renee , Ayers Marie , Bell Christina , Bracewell Emily , Crabtree Patricia , Holder Carolyn , Kaplow Roberta , Whitson Margaret
Published: November 2020

Background: Hospital-acquired methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA BSIs) are associated with serious morbidity and mortality in immunocompromised patients. Of all MRSA BSIs at our academic medical center, 63% occurred in the oncology units. A multidisciplinary team was formed to address the improvement opportunity: the clinical nurse specialist, hospital epidemiologist, unit leaders, nurse champions and representatives from infection prevention, pharmacy and information technology. The goal was to decrease the incidence of hospital-onset MRSA BSI in the oncology wards by 10 infections in 2016 by implementing daily chlorohexidine (CHG) bathing and weekly nasal povidone-iodine antisepsis in July 2016. Methods: The strategically targeting oncology with povidone-iodine nasal antisepsis and bathing with CHG Staph reduction initiative (STOP-BSI) was a quality improvement project consisting of daily CHG baths for all oncology patients and nasal povidone-iodine on admission and weekly thereafter. Nurses and patient care technicians were trained on how to administer CHG treatments. Education was also provided to patients on how to use CHG bath wipes to self-administer the nasal antisepsis. Education resources were created to help answer concerns of the staff, patient, or family, and an escalation process was developed for treatment refusal. CHG bath audits were performed to measure compliance and to identify barriers to the process. Results: By the end of 2016, the number of infections decreased by 5 on the oncology units. The number of infections continued to decrease each year. The bone marrow transplant (BMT) unit decreased from 8 infections in 2015 to 3 in 2018. The hematology oncology unit infections decreased from 5 infections in 2015 to 0 in 2018. The medical oncology unit infections decreased from 2 infections in 2015 to 0 in 2018. The CLABSI rates per 1,000 line days trended downward after some time. Conclusions: Implementing daily CHG baths and weekly povidone-iodine nasal antisepsis reduced the number of MRSA BSI infections in the oncology population. The CLABSI rates decreased after barriers to the process were removed.

Funding: None

Disclosures: None
Successful Response to a Measles Exposure in a Pediatric Clinic Utilizing Measles, Mumps, and Rubella (MMR) Vaccine Prophylaxis
Authors: Champsi Jamila , Leong Stephanie
Published: November 2020

Background: To be effective, postexposure prophylaxis (PEP) must be administered promptly after measles exposure. MMR vaccine is recommended within 72 hours of exposure. Immunoglobulin (IG) is recommended for infants aged <6–12 months, susceptible individuals, and severely immunocompromised people within 6 days of exposure. MMR vaccine is readily available, less expensive, and more easily administered than IG, and it provides long-term immunity. However, due to delays in diagnosis of measles cases, it is often not possible to administer MMR PEP to contacts within 72 hours. We describe an unvaccinated infant with fever and rash after recent international travel who presented to a pediatric outpatient clinic. Measles was promptly suspected, and specimens were collected for measles polymerase chain reaction (PCR) testing at the California Department of Public Health (CDPH) laboratory. PCR results confirming measles were obtained within 24 hours of the patient visit. Methods: A multidisciplinary team of medical, employee health, nursing, pharmacy and infection prevention staff was assembled. Electronic health records (EHRs) were used to identify exposed patients based on registration times, as well as to determine their MMR vaccination status and to identify any immunocompromising conditions. Exposed patients were notified either by e-mail or phone. Adult caretakers were interviewed to determine who accompanied the child to the clinic. Caretakers were questioned regarding their MMR vaccination status and the high risk to accompanying persons. The use of EHRs with data integration from other healthcare system helped validate and supplement vaccine statuses and medical histories of exposed family members. Results: In total, 128 persons were exposed; 31 staff (24%), 46 patients (36%) and 51 family members (40$). All 128 patients (100%) and family members were notified within 24 hours of case confirmation, and 44 of 128 (34%) required PEP. All staff had documentation of measles immune status. However, 1 of 31 staff (3%) needed PEP due to immunosuppression. MMR vaccine was given to 35 of 36 eligible persons (97%), except for 1 sibling who received IG due to delay in exposure identification. An additional 8 of 44 persons (18%) required IG due to age or immunosuppression. There were no secondary cases. Conclusions: MMR vaccine was used as primary PEP due to prompt suspicion for measles, early laboratory confirmation, and swift coordinated response using a multidisciplinary team. Leveraging EHRs helped rapidly identify exposed persons, validate measles immunity status and risk factors, order prophylaxis, and track outcomes.

Funding: None

Disclosures: None