bluuebunny/crossref_metadata_2025 huggingface dataset:
Stratification and Heat Transfer of Molten Corium Pool for In-Vessel Retention
Authors: Xiang Qingan , Deng Jian , Zhu Dahuan , Wu Xiaoli , Bi Jinsheng , Chen Baowen , Cai Rong , Qian Libo , Ma Yugao
Published: October 2020

In-vessel retention (IVR) consists in cooling the molten corium contained in the lower head of reactor vessel by natural convection and reactor cavity flooding. The general approach which is used to study IVR problems is a “bounding” approach which consists in assuming a specified corium pool stratification in the vessel and then demonstrating that the vessel can cope with the resulting thermal and mechanical loads. Thermal loading on the vessel is controlled by the convective heat transfer inside the molten corium pool. Traditionally molten corium pool in the lower head was expected to stratify into two-layer with the dense oxide pool at the bottom and the light metal layer on the top. Based on the MASCA experiments, the increased density of the metal layer attributed to a transfer of uranium metal leads to inverse stratification with a heavy metal layer relocating below the oxide pool. This behavior can be explained by physicochemical interaction between the oxidic and metallic phases of the corium pool. Therefore, a methodology which couples physicochemical effects and thermal hydraulics has been developed to address the IVR issue. The main purpose of this paper is to present this methodology and its application for calculate stratification probability of two-layer and three-layer configuration, analyze the safety margin of IVR in two-layer and three-layer configuration, and evaluate the lower head heat thermal failure probability.
Sodium Fire Analysis Using a Sodium Chemistry Package in MELCOR
Authors: Aoyagi Mitsuhiro , Uchibori Akihiro , Takata Takahi , Louie David L. Y. , Clark Andrew J.
Published: October 2020

The Sodium Chemistry (NAC) package in MELCOR has been developed to enhance application to sodium cooled fast reactors. The models in the NAC package have been assessed through benchmark analyses. The F7-1 pool fire experimental analysis is conducted within the framework of the U.S.–Japan collaboration; Civil Nuclear Energy Research and Development Working Group. This study assesses the capability of the pool fire model in MELCOR and provides recommendations for future model improvements because the physics of sodium pool fire are complex. Based on the preliminary results, analytical conditions, such as heat transfer on the floor catch pan are modified. The current MELCOR analysis yields lower values than the experimental data in pool combustion rate and pool, catch pan, and gas temperature during early time. The current treatment of heat transfer for the catch pan is the primary cause of the difference in the results from the experimental data. After sodium discharge stopping, the pool combustion rate and temperature become higher than experimental data. This is caused by absence of a model for pool fire suppression due to the oxide layer buildup on the pool surface. Based on these results, recommendations for future works are needed, such as heat transfer modification in terms of the catch pan and consideration of the effects of the oxide layer for both the MELCOR input model and pool physic.
Heating Impact on Corrosion Mechanism of Carbon Steel Surrounded by Bentonite
Authors: Uyama Masao , Saito Hiroyuki , Iioka Tomoya
Published: October 2020

The long-term safety of geological disposal of radioactive waste is studied through several simulations. Before underground disposal, radioactive waste is stored for 30 to 50 years at facilities near nuclear power plants to cool it down to around 100 degrees. It is then placed in steel canisters surrounded by artificial materials such as bentonite and concrete.

To determine the long-term safety and stability of this disposal method, we’ve studied the corrosion rate of the steel canisters under different conditions using electro-chemical impedance spectroscopy (EIS). This paper describes the corrosion of the carbon steel and elucidates the corroded condition using EIS measurement. EIS was adopted to estimate the corrosion condition from the impedance frequency characteristic.

In our experiment, samples of bentonite and carbon steel were compacted to Kunigel V1 of 1.37Mg/m3 dry density with several different water contents, and SM400 as a low carbon steel inside compacted bentonite. An electric heater was set inside the steel canister to maintain the temperature at 100 degrees Celsius. This model was made to a scale of around 1/120 as a current concept of a vertical disposal plan and reproduced the enclosed situation after underground emplacement of the radioactive waste. During heating, we conducted EIS measurements and set this data result as an equivalent circuit.

We noted some different trends of impedance frequency characteristic depending on the bentonite’s water content and the heating time. From this result, we estimated the corrosion condition to analyze the corrosion products.
Incorporating FLEX Strategies in Multi-Unit Probabilistic Risk Assessment
Authors: Zhang Sai , Ma Zhegang
Published: October 2020

The catastrophic Fukushima nuclear accident reminded the nuclear community about potential extreme accident scenarios, including those involving multiple reactor units on the same site. In response to the Fukushima accident, the nuclear power industry developed and implemented a series of strategies, including Diverse and Flexible Coping Strategies (FLEX), to enhance the capacities of nuclear power plants (NPPs) to cope with extreme accidents. This study examines the impact of FLEX strategies on the overall risk from all reactor units located at the same NPP site, including risks from accidents involving either a single unit or multiple units. The fundamental, methodological element of this study is Multi-Unit Probabilistic Risk Assessment (MUPRA) requiring a shift in Probabilistic Risk Assessment (PRA) from a one-reactor-at-a-time mindset to a consideration of all reactors sharing a site. An integrated modeling approach for multi-unit event sequence development is leveraged to develop the MUPRA model and address intra-unit and inter-unit dependencies. Systems Analysis Programs for Hands-on Integrated Reliability Evaluations (SAPHIRE), a PRA software developed and maintained by Idaho National Laboratory for the United States (U.S.) Nuclear Regulatory Commission, serves as the platform for MUPRA modeling. This study selects loss of offsite power (LOOP) as a representative initiating event potentially occurring on a generic two-unit NPP site and impacting both reactor units. First, an MUPRA model, including multi-unit event trees, is developed to obtain single-unit and multi-unit accident scenarios. Next, different FLEX strategies are assumed; for example, whether FLEX equipment for multiple units can be used in a cross-connected manner. Lastly, the effectiveness of each postulated FLEX strategy is evaluated by incorporating the corresponding FLEX equipment and deployment logic into the MUPRA model.
In-Vessel Core Melt Retention Strategy Applied for the Rivne VVER-440 Unit
Authors: Dubyk Yaroslav , Antonchenko Vitalii
Published: October 2020

In-Vessel Core Melt Retention (IVMR) strategy via external vessel cooling is widely applied for reactors of relatively low power like VVER-440. In this study, IVMR strategy was applied for Rivne-1, 2 units to prove the pressure vessel integrity. Based on initial data like heat flux for internal wall and external wall temperature, a series of calculations for different scenarios were performed. These calculations include non-elastic material properties: creep and plasticity. As the result, the wall ablation, radial displacements, stress and strains were obtained. To prove pressure vessel integrity four criterions have been checked. The first one is obvious — remaining wall thickness, to prove that that RPV won’t be melted right through. The second one is visco-plastic collapse — lack of monotonous increase in deformations, in case of FEM solution result convergence can be interpreted as resist against such failure. The third — sustainable external cooling, thus the gap between RPV (due to radial elongation) and thermal protection shield must be 10 mm at least. The last one is brittle strength, this calculation was performed on a separate model.
Are Genome-Wide Association Study Identified Single-Nucleotide Polymorphisms Associated With Sprint Athletic Status? A Replication Study With 3 Different Cohorts
Authors: Guilherme João Paulo Limongi França , Semenova Ekaterina A. , Zempo Hirofumi , Martins Gabriel L. , Lancha Junior Antonio H. , Miyamoto-Mikami Eri , Kumagai Hiroshi , Tobina Takuro , Shiose Keisuke , Kakigi Ryo , Tsuzuki Takamasa , Ichinoseki-Sekine Noriko , Kobayashi Hiroyuki , Naito Hisashi , Borisov Oleg V. , Kostryukova Elena S. , Kulemin Nikolay A. , Larin Andrey K. , Generozov Edward V. , Fuku Noriyuki , Ahmetov Ildus I.
Published: October 2020

Purpose: To replicate previous genome-wide association study identified sprint-related polymorphisms in 3 different cohorts of top-level sprinters and to further validate the obtained results in functional studies. Methods: A total of 240 Japanese, 290 Russians, and 593 Brazilians were evaluated in a case-control approach. Of these, 267 were top-level sprint/power athletes. In addition, the relationship between selected polymorphisms and muscle fiber composition was evaluated in 203 Japanese and 287 Finnish individuals. Results: The G allele of the rs3213537 polymorphism was overrepresented in Japanese (odds ratio [OR]: 2.07, P = .024) and Russian (OR: 1.93, P = .027) sprinters compared with endurance athletes and was associated with an increased proportion of fast-twitch muscle fibers in Japanese (P = .02) and Finnish (P = .041) individuals. A meta-analysis of the data from 4 athlete cohorts confirmed that the presence of the G/G genotype rather than the G/A+A/A genotypes increased the OR of being a sprinter compared with controls (OR: 1.49, P = .01), endurance athletes (OR: 1.79, P = .001), or controls + endurance athletes (OR: 1.58, P = .002). Furthermore, male sprinters with the G/G genotype were found to have significantly faster personal times in the 100-m dash than those with G/A+A/A genotypes (10.50 [0.26] vs 10.76 [0.31], P = .014). Conclusion: The rs3213537 polymorphism found in the CPNE5 gene was identified as a highly replicable variant associated with sprinting ability and the increased proportion of fast-twitch muscle fibers, in which the homozygous genotype for the major allele (ie, the G/G genotype) is preferable for performance.
Where to Place Which Sensor to Measure Sedentary Behavior? A Method Development and Comparison Among Various Sensor Placements and Signal Types
Authors: Kuster Roman P. , Baumgartner Daniel , Hagströmer Maria , Grooten Wilhelmus J.A.
Published: October 2020

Background: Sedentary behavior (SB) is associated with several chronic diseases and office workers especially are at increased risk. SB is defined by a sitting or reclined body posture with an energy expenditure of ≤1.5 metabolic equivalents. However, current objective methods to measure SB are not consistent with its definition. There is no consensus on which sensor placement and type should be used. Aim: To compare the accuracy of newly developed artificial intelligence models for 15 sensor placements in combination with four signal types (accelerometer only/plus gyroscope and/or magnetometer) to detect posture and physical in-/activity during desk-based activities. Method: Signal features for the model development were extracted from sensor raw data of 30 office workers performing 10 desk-based tasks, each lasting 5 min. Direct observation (posture) and indirect calorimetry (in-/activity) served as the reference criteria. The best classification model for each sensor was identified and compared among the sensor placements, both using Friedman and post hoc Wilcoxon tests (p ≤ .05). Results: Posture was most accurately measured with a lower body sensor, while in-/activity was most accurately measured with an upper body or waist sensor. The inclusion of additional signal types improved the posture classification for some placements, while the acceleration signal already contained the relevant signal information for the in-/activity classification. Overall, the thigh accelerometer most accurately classified desk-based SB. Conclusion: This study favors, in line with previous work, the measurement of SB with a thigh-worn accelerometer and adds the information that this sensor is also accurate in measuring physical in-/activity while sitting and standing.
Relationship Between Sedentary Behavior and Physical Activity at Work and Cognition and Mood
Authors: Carter Sophie E. , Draijer Richard , Thompson Andrew , Thijssen Dick H.J. , Hopkins Nicola D.
Published: October 2020

Background: Sedentary behavior is negatively associated with cognition and mood. Adults often engage in high levels of sedentary behavior at work through sitting, which may impact productivity. Consequently, replacing sitting with standing and physical activity (PA) is recommended. However, the associations between sitting, standing, and PA at work and cognition and mood are unknown; this study, therefore, aimed to explore these relationships. Methods: A total of 75 healthy full-time workers (33 male, mean [SD]; 33.6 [10.4] y, 38 [7] work hr/wk) wore sedentary behavior (activPAL) and PA (SenseWear Pro) monitors for 7 days and recorded their work hours. The day after this monitoring period, participants completed cognitive tests (executive function, attention, and working memory) and mood questionnaires (affect, alert, content, and calm). Multiple linear regression analyses examined the associations between cognition and mood and the time spent sitting, standing, and in each PA intensity during work hours, weekday leisure time, and weekends. Results: Workplace sitting, standing, or PA were not significantly associated with cognition or mood (P > .05). No significant associations were observed between these variables during weekday leisure time or weekends (P > .05). Conclusions: In a cohort of healthy workers, workplace sitting, standing, and PA are not associated with cognition or mood. Further research in this population is needed, examining the influence of workplace behaviors on cognition and mood, because this will contribute to evidence-based workplace guidelines to increase productivity.
An Analysis of Training-Related Outcomes Within Canadian National Sport Organizations
Authors: Millar Patti , Stevens Julie
Published: October 2020

Past research has demonstrated that human resource training often results in improved individual and organizational performances. Yet, the focus has been on whether or not training has an impact on performance, rather than the nature of that impact. The purpose of this study is to investigate the nature of training-related outcomes in the context of one training program within the Canadian national sport sector. Interviews were conducted with key representatives from 12 Canadian national sport organizations. Findings showed the manifestations of performance change that occur as a result of training, revealing a new way of thinking at the individual level, a new way of doing within group and organizational processes, and a new way of being across organizations. Three theoretical perspectives—interpretation, learning, and institutional—are used to frame the discussion of the findings. Implications for practice and future research are presented.
Cerebrospinal Fluid Penetration of Ceftolozane-Tazobactam in Critically Ill Patients with an Indwelling External Ventricular Drain
Authors: Sime Fekade B. , Lassig-Smith Melissa , Starr Therese , Stuart Janine , Pandey Saurabh , Parker Suzanne L. , Wallis Steven C. , Lipman Jeffrey , Roberts Jason A.
Published: October 2020

The aim of this study was to describe the pharmacokinetics of ceftolozane-tazobactam in plasma and cerebrospinal fluid (CSF) of infected critically ill patients. In a prospective observational study, critically ill patients (≥18 years) with an indwelling external ventricular drain received a single intravenous dose of 3.0 g ceftolozane-tazobactam. Serial plasma and CSF samples were collected for measurement of unbound ceftolozane and tazobactam concentration by liquid chromatography.
Friend or Foe: Interbacterial Competition in the Nasal Cavity
Authors: Hardy Britney L. , Merrell D. Scott
Published: October 2020

Like other microbes that live on or in the human body, the bacteria that inhabit the upper respiratory tract, in particular the nasal cavity, have evolved to survive in an environment that presents a number of physical and chemical challenges; these microbes are constantly bombarded with nutritional fluctuations, changes in humidity, the presence of inhaled particulate matter (odorants and allergens), and competition with other microbes. Indeed, only a specialized set of species is able to colonize this niche and successfully contend with the host’s immune system and the constant threat from competitors.
COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva
Authors: Pisanic Nora , Randad Pranay R. , Kruczynski Kate , Manabe Yukari C. , Thomas David L. , Pekosz Andrew , Klein Sabra L. , Betenbaugh Michael J. , Clarke William A. , Laeyendecker Oliver , Caturegli Patrizio P. , Larman H. Benjamin , Detrick Barbara , Fairley Jessica K. , Sherman Amy C. , Rouphael Nadine , Edupuganti Srilatha , Granger Douglas A. , Granger Steve W. , Collins Matthew H. , Heaney Christopher D.
Published: October 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale.
Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015
Authors: Hemelaar Joris , Loganathan Shanghavie , Elangovan Ramyiadarsini , Yun Jason , Dickson-Tetteh Leslie , Kirtley Shona ,   WHO-UNAIDS Network for HIV Isolation and Characterization
Published: October 2020

This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays.
Multiplex CRISPRi System Enables the Study of Stage-Specific Biofilm Genetic Requirements in Enterococcus faecalis
Authors: Afonina Irina , Ong June , Chua Jerome , Lu Timothy , Kline Kimberly A.
Published: October 2020

Enterococcus faecalis
causes multidrug-resistant life-threatening infections and is often coisolated with other pathogenic bacteria from polymicrobial biofilm-associated infections. Genetic tools to dissect complex interactions in mixed microbial communities are largely limited to transposon mutagenesis and traditional time- and labor-intensive allelic-exchange methods. Built upon streptococcal dCas9, we developed an easily modifiable, inducible CRISPRi system for
E. faecalis
that can efficiently silence single and multiple genes. This system can silence genes involved in biofilm formation and antibiotic resistance and can be used to interrogate gene essentiality. Uniquely, this tool is optimized to study genes important for biofilm initiation, maturation, and maintenance and can be used to perturb preformed biofilms. This system will be valuable to rapidly and efficiently investigate a wide range of aspects of complex enterococcal biology.
A Giant Extracellular Matrix Binding Protein of
Staphylococcus epidermidis
Binds Surface-Immobilized Fibronectin via a Novel Mechanism
Authors: Büttner Henning , Perbandt Markus , Kohler Thomas , Kikhney Alexey , Wolters Manuel , Christner Martin , Heise Marisol , Wilde Jérôme , Weißelberg Samira , Both Anna , Betzel Christian , Hammerschmidt Sven , Svergun Dmitri , Aepfelbacher Martin , Rohde Holger
Published: October 2020

Staphylococcus epidermidis
is a leading pathogen in implant-associated hospital infections. The pathogenesis critically depends on bacterial binding to ECM components, specifically fibronectin (Fn). The cell surface-localized, 1-MDa extracellular matrix binding protein (Embp) is essentially characterized by 10 F- and 40 FG-repeats. These repetitive units, each characterized by two α-helical bundles, organize themselves in a rigid, elongated form. Embp binds preferentially to surface-localized but not soluble Fn, with both F- and FG-repeats being sufficient for Fn binding and resulting bacterial adherence. Binding preferentially involves Fn type III domain, specifically residues of FN12 β-sheets C and F. Both play key role in stabilizing the globular Fn conformation, explaining the necessity of Fn surface immobilization for a subsequent interaction with Embp. In comparison to many other bacterial Fn-binding proteins using the Fn N terminus, Embp employs a previously undescribed mechanism supporting the adhesion of
S. epidermidis
to surface-immobilized Fn.
Immune Response and Microbiota Profiles during Coinfection with Plasmodium vivax and Soil-Transmitted Helminths
Authors: Easton Alice V. , Raciny-Aleman Mayra , Liu Victor , Ruan Erica , Marier Christian , Heguy Adriana , Yasnot Maria Fernanda , Rodriguez Ana , Loke P’ng
Published: October 2020

Plasmodium
(malaria) and helminth parasite coinfections are frequent, and both infections can be affected by the host gut microbiota. However, the relationship between coinfection and the gut microbiota is unclear. By performing comprehensive analyses on blood/stool samples from 130 individuals in Colombia, we found that the gut microbiota may have a stronger relationship with the number of
P. vivax
(malaria) parasites than with the number of helminth parasites infecting a host. Microbiota analysis identified more predictors of the
P. vivax
parasite burden, whereas analysis of blood samples identified predictors of the helminth parasite burden. These results were unexpected, because we expected each parasite to be associated with greater differences in its biological niche (blood for
P. vivax
and the intestine for helminths). Instead, we find that bacterial taxa were the strongest predictors of
P. vivax
parasitemia levels, while circulating TGF-β levels were the strongest predictor of helminth parasite burdens.
Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals
Authors: Beaudoin-Bussières Guillaume , Laumaea Annemarie , Anand Sai Priya , Prévost Jérémie , Gasser Romain , Goyette Guillaume , Medjahed Halima , Perreault Josée , Tremblay Tony , Lewin Antoine , Gokool Laurie , Morrisseau Chantal , Bégin Philippe , Tremblay Cécile , Martel-Laferrière Valérie , Kaufmann Daniel E. , Richard Jonathan , Bazin Renée , Finzi Andrés
Published: October 2020

While waiting for an efficient vaccine to protect against SARS-CoV-2 infection, alternative approaches to treat or prevent acute COVID-19 are urgently needed. Transfusion of convalescent plasma to treat COVID-19 patients is currently being explored; neutralizing activity in convalescent plasma is thought to play a central role in the efficacy of this treatment. Here, we observed that plasma neutralization activity decreased a few weeks after the onset of the symptoms. If neutralizing activity is required for the efficacy of convalescent plasma transfer, our results suggest that convalescent plasma should be recovered rapidly after the donor recovers from active infection.
Gut Microbiota and Host Thermoregulation in Response to Ambient Temperature Fluctuations
Authors: Khakisahneh Saeid , Zhang Xue-Ying , Nouri Zahra , Wang De-Hua
Published: October 2020

Whether gut microbiota play a role in regulating host phenotypic plasticity in small mammals living in seasonal environments has rarely been examined. The present study, through an intermittent temperature acclimation model, indicates that both gut microbiota and their host were more adaptive after repeated acclimations. It also demonstrates that dynamic gut microbiota confer host plasticity in thermoregulation in response to intermittent temperature fluctuations. Furthermore, low temperature seems to be a crucial cue in driving the symbiosis between mammals and their gut microbiota during evolution.
Aflibercept ameliorates retinal pericyte loss and restores perfusion in streptozotocin-induced diabetic mice
Authors: Seo Eoi Jong , Choi Jeong A , Koh Jae-Young , Yoon Young Hee
Published: October 2020

Introduction

Anti-vascular endothelial growth factor (VEGF) agents are used worldwide for advanced-stage diabetic retinopathy (DR). In contrast, apart from blood glucose control, there are no specific treatments that can limit the progression of early-stage DR that starts with pericyte loss and the destruction of the blood–retinal barrier. Here, we examined the efficacy of aflibercept, a potent anti-VEGF agent, against early-DR pathologies in a murine model of streptozotocin (STZ)-induced DR.

Research design and methods

STZ was intraperitoneally administered in 8-week-old C57BL/6N male mice. After 4 weeks, the mice were divided into aflibercept-treated and saline-treated groups. Eight weeks after the STZ injection, vascular permeability/leakage was measured with fluorescein angiography in live mice. At 4, 6, and 8 weeks after the STZ injection, the eyes were enucleated, flat-mounted, and stained for platelet-derived growth factor receptor-β to assess pericyte abundance, CD45 to assess leukocyte recruitment, and fluorescein isothiocyanate dextran to assess perfusion. VEGF levels were quantified in each group. The effects of aflibercept on pericyte number, perfusion status, and leukocyte recruitment/accumulation on mice with diabetes retina were evaluated.

Results

Our murine model successfully replicated the salient pathologies of DR such as pericytes loss, hyperpermeability, and perfusion blockage. Interestingly, numerous leukocytes and leukocyte clumps were found in diabetic retinal capillaries, especially in the non-perfused border area of the retina, suggesting a possible mechanism for non-perfusion and related pericyte damage. Treatment with aflibercept in mice with diabetes inhibited the upregulation of VEGF and the associated adhesion molecules while reducing the defects in perfusion. Aflibercept also attenuated pericyte loss in the diabetic retina.

Conclusion

VEGF inhibition through aflibercept treatment decreased leukocyte recruitment and aggregation, perfusion blockage, retinal hypoperfusion, and hyperpermeability in mice with diabetes and ultimately attenuated pericyte loss. Our findings suggest that anti-VEGF strategies may prove useful as possible therapies for limiting the progression of early-stage DR.
Impaired glucose regulation, depressive symptoms, and health-related quality of life
Authors: Selenius Jannica S , Wasenius Niko S , Kautiainen Hannu , Salonen Minna , von Bonsdorff Mikaela , Eriksson Johan G
Published: October 2020

Introduction

This study aims to investigate whether the associations between impaired glucose regulation and health-related quality of life are modified by severity or type of depressive symptoms.

Research design and methods

For this cross-sectional study, we included 1939 individuals (mean age 61.5 years) from the Helsinki Birth Cohort Study. Between 2001 and 2004, a standard 2-hour 75 g oral glucose tolerance test was applied to define normoglycemia, pre-diabetes, and newly diagnosed diabetes. Information on previously diagnosed diabetes was collected from national registers and questionnaires. Pre-diabetes was defined as having either impaired fasting glucose or impaired glucose tolerance. The Mental and Physical Component Scores of health-related quality of life were assessed with Short Form-36. Beck’s Depression Inventory was employed to investigate the severity of depressive symptoms and to define minimal (depression score <10), non-melancholic, and melancholic types of depression. We analyzed data with general linear models adjusted for sex, age, lifestyle factors, comorbidities, and body mass index.

Results

Glucose regulation subgroups, especially previously known diabetes, were associated with lower Physical Component Score (p=0.001) and higher depression score (p=0.015), but not with the Mental Component Score (p=0.189). Non-melancholic depression was associated with lower Physical and Mental Component Scores compared with those with depression score <10 and melancholic depression (p<0.001), independently of glucose regulation status (p for glucose regulation status by depression type interaction >0.54).

Conclusions

Non-melancholic type of depression and previously known diabetes are independently associated with lower health-related quality of life. This should be appraised in long-term treatment of diabetes and when treating non-melancholic depressive symptoms to maintain a higher health-related quality of life.
Prognostic models for predicting in-hospital paediatric mortality in resource-limited countries: a systematic review
Authors: Ogero Morris , Sarguta Rachel Jelagat , Malla Lucas , Aluvaala Jalemba , Agweyu Ambrose , English Mike , Onyango Nelson Owuor , Akech Samuel
Published: October 2020

Objectives

To identify and appraise the methodological rigour of multivariable prognostic models predicting in-hospital paediatric mortality in low-income and middle-income countries (LMICs).

Design

Systematic review of peer-reviewed journals.

Data sources

MEDLINE, CINAHL, Google Scholar and Web of Science electronic databases since inception to August 2019.

Eligibility criteria

We included model development studies predicting in-hospital paediatric mortality in LMIC.

Data extraction and synthesis

This systematic review followed the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies framework. The risk of bias assessment was conducted using Prediction model Risk of Bias Assessment Tool (PROBAST). No quantitative summary was conducted due to substantial heterogeneity that was observed after assessing the studies included.

Results

Our search strategy identified a total of 4054 unique articles. Among these, 3545 articles were excluded after review of titles and abstracts as they covered non-relevant topics. Full texts of 509 articles were screened for eligibility, of which 15 studies reporting 21 models met the eligibility criteria. Based on the PROBAST tool, risk of bias was assessed in four domains; participant, predictors, outcome and analyses. The domain of statistical analyses was the main area of concern where none of the included models was judged to be of low risk of bias.

Conclusion

This review identified 21 models predicting in-hospital paediatric mortality in LMIC. However, most reports characterising these models are of poor quality when judged against recent reporting standards due to a high risk of bias. Future studies should adhere to standardised methodological criteria and progress from identifying new risk scores to validating or adapting existing scores.

PROSPERO registration number

CRD42018088599.
Safety of furazolidone-containing regimen in Helicobacter pylori infection: a systematic review and meta-analysis
Authors: Ji Chao-ran , Liu Jing , Li Yue-yue , Guo Chuan-guo , Qu Jun-yan , Zhang Yan , Zuo Xiuli
Published: October 2020

Objectives

Furazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection.

Design

A systematic review and meta-analysis.

Data sources

PubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials.

Eligibility criteria

Studies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included.

Data extraction and synthesis

Two reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance.

Results

Twenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments.

Conclusion

Furazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered.

PROSPERO registration number

CRD42019137247
Benefits finding among Chinese family caregivers of stroke survivors: a qualitative descriptive study
Authors: Mei Yong-Xia , Lin Beilei , Zhang Weihong , Yang Dong-Bin , Wang Shan-Shan , Zhang Zhen-Xiang , Cheung Daphne Sze Ki
Published: October 2020

Objectives

The caregiving experience includes both caregiver burdens and benefits finding. However, the benefits obtained by family caregivers of stroke survivors in Chinese community dwellings are unknown. The objective of this study was to explore the benefits experienced by family caregivers of stroke survivors in Chinese community dwellings.

Design

A qualitative descriptive design was used, fulfilling the consolidated criteria for the Standards for Reporting Qualitative Research reporting guidelines. Semi-structured interviews were conducted with 20 family caregivers of stroke survivors. The interviews were audiotaped, transcribed and analysed. Thematic analysis was performed to analyse the interview transcripts.

Setting and participants

Home interviews were conducted with family caregivers of stroke survivors in two communities in Zhengzhou, China.

Results

The family caregivers of stroke survivors experienced various benefits from caregiving. There were both internal benefits (increases in knowledge and skills, the development of positive attitudes, and the development of a sense of worthiness and achievement) and external benefits (family growth and gains in social support), which interact to create a healthy lifestyle.

Conclusion

Our findings provide a comprehensive perspective in understanding the benefits perceived by family caregivers of stroke survivors. This study provides insights into interventions focused on identifying benefits finding in six domains that may help reduce negative emotions and promote the mental health of caregivers.
Risks of use and non-use of antibiotics in primary care: qualitative study of prescribers’ views
Authors: Boiko Olga , Burgess Caroline , Fox Robin , Ashworth Mark , Gulliford Martin C
Published: October 2020

Purpose

The emergence of antimicrobial resistance has led to increasing efforts to reduce unnecessary use of antibiotics in primary care, but potential hazards from bacterial infection continue to cause concern. This study investigated how primary care prescribers perceive risk and safety concerns associated with reduced antibiotic prescribing.

Methods

Qualitative study using semistructured interviews conducted with primary care prescribers from 10 general practices in an urban area and a shire town in England. A thematic analysis was conducted.

Results

Thirty participants were recruited, including twenty-three general practitioners, five nurses and two pharmacists. Three main themes were identified: risk assessment, balancing treatment risks and negotiating decisions and risks. Respondents indicated that their decisions were grounded in clinical risk assessment, but this was informed by different approaches to antibiotic use, with most leaning towards reduced prescribing. Prescribers’ perceptions of risk included the consequences of both inappropriate prescribing and inappropriate withholding of antibiotics. Sepsis was viewed as the most concerning potential outcome of non-prescribing, leading to possible patient harm and potential litigation. Risks of antibiotic prescribing included antibiotic resistant and Clostridium difficile infections, as well as side effects, such as rashes, that might lead to possible mislabelling as antibiotic allergy. Prescribers elicited patient preferences for use or avoidance of antibiotics to inform management strategies, which included educational advice, advice on self-management including warning signs, use of delayed prescriptions and safety netting.

Conclusions

Attitudes towards antibiotic prescribing are evolving, with reduced antibiotic prescribing now being approached more systematically. The safety trade-offs associated with either use or non-use of antibiotics present difficulties especially when prescribing decisions are inconsistent with patients’ expectations.
Vaping-related injury and illness among Canadian children and adolescents: a one-time survey of paediatric providers
Authors: Chadi Nicholas , Moore-Hepburn Charlotte , Beno Suzanne , Richmond Sarah A
Published: October 2020

A one-time survey distributed to 2693 Canadian paediatricians enrolled in the Canadian Paediatric Surveillance Programme was conducted between October and December 2019. We identified a wide range of severe vaping-related injuries and illnesses among children ages 0–17 (n=88), which were associated with the routine use or malfunctioning of a vaping device or the ingestion of vaping substances. The most common clinical presentations were acute respiratory symptoms and nicotine toxicity and 15% (n=13) of injuries required intensive care unit admission. Our study highlights the urgent need for substantive policy measures to help protect youth against the risks associated with vaping products.
Functional abdominal pain in adolescents: case-based management
Authors: Yacob Desale , Kroon Van Diest Ashley M , Di Lorenzo Carlo
Published: October 2020

Functional gastrointestinal disorders (FGIDs), including functional abdominal pain (FAP), account for a large portion of conditions seen by paediatric gastroenterologists. Despite the commonality of FGIDs, there remains significant stigma around these diagnoses among medical providers, patients and families. This is due to the absence of easily identifiable biological markers in FGIDs and the overlay with psychological and social factors contributing to symptom onset and maintenance. As such, the biopsychosocial model is essential in conceptualising, evaluating and treating FGIDs. The way in which medical providers explain FGIDs and the manner in which they collaborate with other specialists (eg, psychologists, dieticians, physical therapists, school nurses) is paramount to the patient and family acceptance of an FGID diagnosis and the success of subsequent treatment. The following review outlines paediatric FGIDs with a focus on FAP in adolescents, in particular within the context of the biopsychosocial approach to pathophysiology, diagnosis and treatment.
Evaluation and treatment of premature ventricular contractions in heart failure with reduced ejection fraction
Authors: Mulder Bart A , Rienstra Michiel , Blaauw Yuri
Published: October 2020

Premature ventricular complexes (PVCs) are often observed in patients presenting with heart failure with a reduced ejection fraction (HFrEF). PVCs may in some patients be considered to be the cause of heart failure, while in others it may be the consequence of heart failure. PVCs are important prognostic markers in HFrEF. The uncertainty whether PVCs are the cause or effect in HFrEF impacts clinical decision making. In this review, we discuss the complexity of the cause–effect relationship between PVCs and HFrEF. We demonstrate a workflow with the use of a trial period of amiodarone that may discover whether the reduced LVEF is reversible, the symptoms are due to PVCs and whether biventricular pacing can be increased by the reduction of PVCs. The use of non-invasive and invasive (high-density) mapping techniques may help to improve accuracy and efficacy in the treatment of PVC, which will be demonstrated. With these results in mind, we conclude this review highlighting the future directions for PVC research and treatment.
The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia
Authors: Boyiadzis Michael M , Aksentijevich Ivan , Arber Daniel A , Barrett John , Brentjens Renier J , Brufsky Jill , Cortes Jorge , De Lima Marcos , Forman Stephen J , Fuchs Ephraim J , Fukas Linda J , Gore Steven D , Litzow Mark R , Miller Jeffrey S , Pagel John M , Waller Edmund K , Tallman Martin S
Published: October 2020

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia.
Clinical advantage of targeted sequencing for unbiased tumor mutational burden estimation in samples with low tumor purity
Authors: Hong Tae Hee , Cha Hongui , Shim Joon Ho , Lee Boram , Chung Jongsuk , Lee Chung , Kim Nayoung K D , Choi Yoon-La , Hwang Soohyun , Lee Yoomi , Park Sehhoon , Jung Hyun Ae , Kim Ji-Yeon , Park Yeon Hee , Sun Jong-Mu , Ahn Jin Seok , Ahn Myung-Ju , Park Keunchil , Lee Se-Hoon , Park Woong-Yang
Published: October 2020

Background

Tumor mutational burden (TMB) measurement is limited by low tumor purity of samples, which can influence prediction of the immunotherapy response, particularly when using whole-exome sequencing-based TMB (wTMB). This issue could be overcome by targeted panel sequencing-based TMB (pTMB) with higher depth of coverage, which remains unexplored.

Methods

We comprehensively reanalyzed four public datasets of immune checkpoint inhibitor (ICI)-treated cohorts (adopting pTMB or wTMB) to test each biomarker’s predictive ability for low purity samples (cut-off: 30%). For validation, paired genomic profiling with the same tumor specimens was performed to directly compare wTMB and pTMB in patients with breast cancer (paired-BRCA, n=165) and ICI-treated patients with advanced non-small-cell lung cancer (paired-NSCLC, n=156).

Results

Low tumor purity was common (range 30%–45%) in real-world samples from ICI-treated patients. In the survival analyzes of public cohorts, wTMB could not predict the clinical benefit of immunotherapy when tumor purity was low (log-rank p=0.874), whereas pTMB could effectively stratify the survival outcome (log-rank p=0.020). In the paired-BRCA and paired-NSCLC cohorts, pTMB was less affected by tumor purity, with significantly more somatic variants identified at low allele frequency (p<0.001). We found that wTMB was significantly underestimated in low purity samples with a large proportion of clonal variants undetected by whole-exome sequencing. Interestingly, pTMB more accurately predicted progression-free survival (PFS) after immunotherapy than wTMB owing to its superior performance in the low tumor purity subgroup (p=0.054 vs p=0.358). Multivariate analysis revealed pTMB (p=0.016), but not wTMB (p=0.32), as an independent predictor of PFS even in low-purity samples. The net reclassification index using pTMB was 21.7% in the low-purity subgroup (p=0.016).

Conclusions

Our data suggest that TMB characterization with targeted deep sequencing might have potential strength in predicting ICI responsiveness due to its enhanced sensitivity for hard-to-detect variants at low-allele fraction. Therefore, pTMB could act as an invaluable biomarker in the setting of both clinical trials and practice outside of trials based on its reliable performance in mitigating the purity-related bias.
Prediction of death after endovascular thrombectomy in the extended window: a secondary analysis of DEFUSE 3 "
Authors: Taussky Philipp , Agnoletto Guilherme , Grandhi Ramesh , Alexander Matthew D , Wong Ka-Ho , Albers Gregory W , de Havenon Adam
Published: October 2020

Background

The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) clinical trial assessed the use of endovascular thrombectomy (EVT) during the period 6–16 hours after last normal in selected patients. This is a secondary cohort analysis of the DEFUSE 3 data assessing potential predictive variables for mortality in the EVT-treated patients.

Methods

The primary outcome was death within 90 days. Patients who died and those who did not were compared statistically. We developed a predictive score using preprocedural variables that were statistically predictive of death in univariate regression analysis (P<0.1).

Results

Of the 182 patients in the DEFUSE 3 study, 92 (mean age 69 years; 50% male) met our inclusion criteria, and 15.2% of these patients met the primary outcome. Patient age, baseline National Institutes of Health Stroke Scale (NIHSS) score, wake-up stroke, statin use, and history of diabetes were statistically associated with death. Statin use did not improve the prediction score so was excluded. Thus, our model included four predictors, with one point each given for age >75 years, NIHSS ≥20, wake-up stroke, and diabetes, yielding low (0–1), moderate (2), and high (3–4) risk of death. In the low-risk, moderate-risk, and high-risk categories, 2/52 (3.9%), 3/23 (13.0%), and 9/17 (52.9%) of patients died, respectively (P<0.001).

Conclusions

Despite selective inclusion criteria and overwhelming benefit for EVT, a substantial number of EVT patients in DEFUSE 3 died. The preprocedural variables age, NIHSS, wake-up stroke, and diabetes may predict this risk. Our predictive score provides a basis for future research to determine which factors influence lethal outcome after EVT.