bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Central Arterial Hemodynamics in Children: Comparison of Noninvasive and Invasive Measurements
Authors: Cai Tommy Y , Haghighi Marjan M , Roberts Philip A , Mervis Jonathan , Qasem Ahmad , Butlin Mark , Celermajer David S , Avolio Alberto , Skilton Michael R , Ayer Julian G
Published: September 2020

Background

In adults, central systolic blood pressure (cSBP) and augmentation index (cAIx) are independently associated with cardiovascular events and mortality. There is increasing interest in central hemodynamic indices in children. We aimed to assess the accuracy of current techniques against invasive intra-aortic measurements in children.

Methods

Intra-aortic pressure waveforms were recorded with simultaneous brachial, radial, and carotid waveforms in 29 children (6.7 ± 3.9 years old) undergoing cardiac catheterization. Adult and age-appropriate transfer functions (TFs) (brachial adult: b-aTF; radial adult: r-aTF; radial for 8-year-old children: TF8; and radial for 14-year-old children: TF14) were used to synthesize central aortic waveforms from peripheral waveforms calibrated either to invasively or noninvasively recorded BP. Central hemodynamic indices were measured by pulse wave analysis.

Results

cSBP measured from invasively calibrated r-aTF (β = 0.84; intraclass correlation coefficient = 0.91; mean error ± SDD = −1.0 ± 5.0 mm Hg), TF8 (β = 0.78; intraclass correlation coefficient = 0.84; mean error ± SDD = 4.4 ± 5.6 mm Hg), and TF14 (β = 0.82; intraclass correlation coefficient = 0.90; mean error ± SDD = 2.0 ± 4.7 mm Hg)-synthesized central waveforms correlated with and accurately estimated intra-aortic cSBP measurements, while noninvasively calibrated waveforms did not. cAIx derived from TF-synthesized central waveforms did not correlate with intra-aortic cAIx values, and degree of error was TF-dependent.

Conclusions

The currently available r-aTF accurately estimates cSBP with invasive pulse pressure calibration, while age-appropriate TFs do not appear to provide additional benefit. Accuracy of cAIx estimation appears to be TF dependent.
A Systematic Review and Meta-Analysis of the Utility of the Test of Memory Malingering in Pediatric Examinees
Authors: Clark Hilary A , Martin Phillip K , Okut Hayrettin , Schroeder Ryan W
Published: September 2020

Objective

This is the first systematic review and meta-analysis of the Test of Memory Malingering (TOMM) in pediatric examinees. It adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Method

A systematic literature search was conducted using PsycINFO and PubMed, reviewing articles from January 1997 to July 2019. Books providing data on pediatric validity testing were also reviewed for references to relevant articles. Eligibility criteria included publication in a peer-reviewed journal, utilizing a pediatric sample, providing sufficient data to calculate specificity and/or sensitivity, and providing a means for evaluating validity status external to the TOMM. After selection criteria were applied, 9 articles remained for meta-analysis. Samples included clinical patients and healthy children recruited for research purposes; ages ranged from 5 to 18. Fixed and random effects models were used to calculate classification accuracy statistics.

Results

Traditional adult-derived cutoffs for Trial 2 and Retention were highly specific (0.96–0.99) in pediatric examinees for both clinical and research samples. Sensitivity was relatively strong (0.68–0.70), although only two studies reported sensitivity rates. A supplemental review of the literature corroborated these findings, revealing that traditional adult-based TOMM cutoffs are supported in most pediatric settings. However, limited research exists on the impact of very young age, extremely low cognitive functioning, and varying clinical diagnoses.

Conclusions

The TOMM, at traditional adult cutoffs, has strong specificity as a performance validity test in pediatric neuropsychological evaluations. This meta-analysis found that specificity values in children are comparable to those of adults. Areas for further research are discussed.
Sequencing dropout-and-batch effect normalization for single-cell mRNA profiles: a survey and comparative analysis
Authors: Lan Tian , Hutvagner Gyorgy , Lan Qing , Liu Tao , Li Jinyan
Published: September 2020

Single-cell mRNA sequencing has been adopted as a powerful technique for understanding gene expression profiles at the single-cell level. However, challenges remain due to factors such as the inefficiency of mRNA molecular capture, technical noises and separate sequencing of cells in different batches. Normalization methods have been developed to ensure a relatively accurate analysis. This work presents a survey on 10 tools specifically designed for single-cell mRNA sequencing data preprocessing steps, among which 6 tools are used for dropout normalization and 4 tools are for batch effect correction. In this survey, we outline the main methodology for each of these tools, and we also compare these tools to evaluate their normalization performance on datasets which are simulated under the constraints of dropout inefficiency, batch effect or their combined effects. We found that Saver and Baynorm performed better than other methods in dropout normalization, in most cases. Beer and Batchelor performed better in the batch effect normalization, and the Saver–Beer tool combination and the Baynorm–Beer combination performed better in the mixed dropout-and-batch effect normalization. Over-normalization is a common issue occurred to these dropout normalization tools that is worth of future investigation. For the batch normalization tools, the capability of retaining heterogeneity between different groups of cells after normalization can be another direction for future improvement.
Burden of Culture Confirmed Enteric Fever Cases in Karachi, Pakistan: Surveillance For Enteric Fever in Asia Project (SEAP), 2016–2019
Authors: Yousafzai Mohammad T , Irfan Seema , Thobani Rozina S , Kazi Abdul M , Hotwani Aneeta , Memon Ashraf M , Iqbal Khalid , Qazi Saqib H , Saddal Nasir S , Rahman Najeeb , Dehraj Irum F , Hunzai Mohammed J , Mehmood Junaid , Garrett Denise O , Saha Samir K , Andrews Jason R , Luby Stephen P , Qamar Farah N
Published: September 2020

Background

The Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan.

Methods

During September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected or confirmed enteric fever cases.

Results

Overall, 22% (2230/10 094) of patients enrolled were culture-positive for enteric fever. 94% (2093/2230) of isolates were Salmonella Typhi and 6% (137/2230) were S. Paratyphi. 15% of isolates multi-drug resistant (MDR) to first-line antibiotics and 60% were extensively drug-resistant (XDR), resistant to first-line antibiotics, fluoroquinolones and third generation cephalosporin.

Conclusion

Enteric fever cases have increased during the last 3 years with large proportion of drug resistant S. Typhi cases. However, the burden of paratyphoid is still relatively low. Strengthening the existing surveillance system for enteric fever and antimicrobial resistance at the national level is recommended in Pakistan to inform prevention measures. While typhoid vaccination can significantly decrease the burden of typhoid and may also impact antimicrobial resistance, water, sanitation, and hygiene improvement is highly recommended to prevent the spread of enteric fever.
Reconsidering Assumptions of Adolescent and Young Adult Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Dynamics
Authors: Guilamo-Ramos Vincent , Benzekri Adam , Thimm-Kaiser Marco , Hidalgo Andrew , Perlman David C
Published: September 2020

Evidence regarding the important role of adolescents and young adults (AYA) in accelerating and sustaining coronavirus disease 2019 (COVID-19) outbreaks is growing. Furthermore, data suggest that 2 known factors that contribute to high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissibility—presymptomatic transmission and asymptomatic case presentations—may be amplified in AYA. However, AYA have not been prioritized as a key population in the public health response to the COVID-19 pandemic. Policy decisions that limit public health attention to AYA and are driven by the assumption of insignificant forward transmission from AYA pose a risk of inadvertent reinvigoration of local transmission dynamics. In this viewpoint, we highlight evidence regarding the increased potential of AYA to transmit SARS-CoV-2 that, to date, has received little attention, discuss adolescent and young adult–specific considerations for future COVID-19 control measures, and provide applied programmatic suggestions.
Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety?
Authors: Dilworth Thomas J , Schulz Lucas T , Rose Warren E
Published: September 2020

Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.
Ventricular arrhythmia risk is associated with myocardial scar but not with response to cardiac resynchronization therapy
Authors: Linhart Markus , Doltra Adelina , Acosta Juan , Borràs Roger , Jáuregui Beatriz , Fernández-Armenta Juan , Anguera Ignasi , Bisbal Felipe , Martí-Almor Julio , Tolosana Jose M , Penela Diego , Soto-Iglesias David , Villuendas Roger , Perea Rosario J , Ortiz Jose T , Bosch Xavier , Auricchio Angelo , Mont Lluis , Berruezo Antonio
Published: September 2020

Aims

Sudden cardiac death (SCD) risk estimation in patients referred for cardiac resynchronization therapy (CRT) remains a challenge. By CRT-mediated improvement of left ventricular ejection fraction (LVEF), many patients loose indication for primary prevention implantable cardioverter-defibrillator (ICD). Increasing evidence shows the importance of myocardial scar for risk prediction. The aim of this study was to investigate the prognostic impact of myocardial scar depending on the echocardiographic response in patients undergoing CRT.

Methods and results

Patients with indication for CRT were prospectively enrolled. Decision about ICD or pacemaker implantation was based on clinical criteria. All patients underwent delayed-enhancement cardiac magnetic resonance imaging. Median follow-up duration was 45 (24–75) months. Primary outcome was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, or SCD. A total of 218 patients with LVEF 25.5 ± 6.6% were analysed [158 (73%) male, 64.9 ± 10.7 years]. Myocardial scar was observed in 73 patients with ischaemic cardiomyopathy (ICM) (95% of ICM patients); in 62 with non-ischaemic cardiomyopathy (45% of these patients); and in all but 1 of 36 (17%) patients who reached the primary outcome. Myocardial scar was the only significant predictor of primary outcome [odds ratio 27.7 (3.8–202.7)], independent of echocardiographic CRT response. A total of 55 (25%) patients died from any cause or received heart transplant. For overall survival, only a combination of the absence of myocardial scar with CRT response was associated with favourable outcome.

Conclusion

Malignant arrhythmic events and SCD depend on the presence of myocardial scar but not on CRT response. All-cause mortality improved only with the combined absence of myocardial scar and CRT response.
Herring Trade, Quality Controls and Diplomacy in Cologne in the Fifteenth Century*
Authors: Brunmayr Nicolas
Published: September 2020

The importance of herring to Cologne’s medieval economy is well-known and the need to control the quality of this long-distance and perishable product has also been widely recognized. The interregional quality norms that Cologne negotiated with Low Countries fishing towns in 1481 have been neglected, however. This article offers the first reconstruction of the diplomatic process that led to the edict and an analysis of the motives that impelled the diverse stakeholders to reach an agreement. The article demonstrates that in addition to herring’s commercial significance, its quality control was a major issue and was used as an instrument of influence by Cologne and other powers in the politically decentralized Holy Roman Empire. Comprehensive analysis of Cologne’s abundant sources shows how exchanges of letters and complaints gradually fed into formal negotiations, culminating in the publication of a crucial edict that established an interregional quality control system and took account of the interests of the different stakeholders in the herring trade. The article suggests that this push for regulation was also an element of Cologne’s economic strategy since it helped justify the taxes the city levied on goods in transit at the expense of competing actors in the Rhine region. In short, the example of quality controls on herring shows how food trade studies can shed light on power relations in the Empire during the late Middle Ages.
Predictors of Olfactory Decline in Aging: A Longitudinal Population-Based Study
Authors: Ekström Ingrid , Larsson Maria , Rizzuto Debora , Fastbom Johan , Bäckman Lars , Laukka Erika J
Published: September 2020

Background

Olfactory dysfunction is common in aging and associated with dementia and mortality. However, longitudinal studies tracking change in olfactory ability are scarce. We sought to identify predictors of interindividual differences in rate of olfactory identification change in aging.

Method

Participants were 1780 individuals, without dementia at baseline and with at least 2 olfactory assessments over 12 years of follow-up (mean age = 70.5 years; 61.9% female), from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Odor identification was assessed with the Sniffin’ Sticks. We estimated the impact of demographic, health, and genetic factors on rate of olfactory change with linear mixed effect models.

Results

Advancing age, manufacturing profession, history of cerebrovascular disease, higher cardiovascular disease burden, diabetes, slower walking speed, higher number of medications, and the APOE ε4 allele were associated with accelerated odor identification decline (ps < .014). Multi-adjusted analyses showed unique associations of age, diabetes, and ε4 to olfactory decline (ps < .017). In 1531 participants who remained free of dementia (DSM IV criteria) during follow-up, age, cardiovascular disease burden, and diabetes were associated with accelerated decline (ps < .011). Of these, age and diabetes remained statistically significant in the multi-adjusted model (ps < .001).

Conclusion

Demographic, vascular, and genetic factors are linked to rate of decline in odor identification in aging. Although some olfactory loss may be an inevitable part of aging, our results highlight the importance of vascular factors for the integrity of the olfactory system, even in the absence of dementia.
Anticholinergic/Sedative Drug Burden and Subjective Cognitive Decline in Older Adults at Risk of Alzheimer’s Disease
Authors: Margolis Seth A , Kelly Dana A , Daiello Lori A , Davis Jennifer , Tremont Geoffrey , Pillemer Sarah , Denby Charles , Ott Brian R
Published: September 2020

Background

Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), has been linked to cognitive impairment in older adults. Subjective cognitive decline (SCD) may be among the first symptoms patients with Alzheimer’s disease (AD) experience. We examined whether DBI values are associated with SCD in older adults at risk of AD. We hypothesized that increased DBI would be associated with greater SCD at older ages.

Method

Two-hundred-six community-dwelling, English-speaking adults (age = 65 ± 9 years) at risk of AD (42% apolipoprotein ε4 carriers; 78% with AD family history) were administered a single question to ascertain SCD: “Do you feel like your memory is becoming worse?” Response options were “No”; “Yes, but this does not worry me”; and “Yes, this worries me.” DBI values were derived from self-reported medication regimens using older adult dosing recommendations. Adjusting for relevant covariates (comorbidities and polypharmacy), we examined independent effects of age and DBI on SCD, as well as the moderating effect of age on the DBI-SCD association at mean ± 1 SD of age.

Results

Both SCD and anticholinergic/sedative drug burden were prevalent. Greater drug burden was predictive of SCD severity, but age alone was not. A significant DBI*Age interaction emerged with greater drug burden corresponding to more severe SCD among individuals age 65 and older.

Conclusion

Anticholinergic/sedative drug exposure was associated with greater SCD in adults 65 and older at risk for AD. Longitudinal research is needed to understand if this relationship is a pre-clinical marker of neurodegenerative disease and predictive of future cognitive decline.
White Blood Cell Count Mediates the Association Between Periodontal Inflammation and Cognitive Performance Measured by Digit Symbol Substitution Test Among Older U.S. Adults
Authors: Li An , Chen Yuntao , van der Sluis Luc W M , Schuller Annemarie A , Tjakkes Geerten-Has
Published: September 2020

Background

Systemic effects of periodontal infection may increase the risk of central neuroinflammation, aggravating impaired cognition. This study aims to examine whether systemic inflammatory factors mediate the possible association between periodontal inflammation and cognitive function.

Methods

We conducted a cross-sectional analysis of 766 participants aged ≥ 60 years and who had completed periodontal and cognitive examinations in the National Health and Nutrition Examination Survey (NHANES) 2001–2002. We used multivariable linear regression to investigate the overall association between periodontal health and cognitive function as measured by the digit symbol substitution test (DSST). Bleeding on probing (BOP) and periodontal inflamed surface area (PISA) were used to assess the periodontal inflammatory activity and burden, respectively. Mediation analyses were used to test the indirect effects of the BOP/PISA on DSST via C-reactive protein, white blood cell (WBC) count, and fibrinogen.

Results

Participants with superior periodontal health obtained higher DSST scores than those with poorer periodontal health, adjusting for demographic factors and chronic conditions. Concerning the inflammatory activity, WBC count acted as a full mediator in the association between BOP and DSST (β = −0.091; 95% confidence interval [CI] = −0.174 to −0.008) and mediated 27.5% of the total association. Regarding the inflammatory burden, WBC count acted as a partial mediator in the association between PISA and DSST (β = −0.059; 95% CI = −0.087 to −0.031) and mediated 20.3% of the total association.

Conclusion

Our study indicated the potential role of systemic inflammatory factors as a mediator of associations between periodontal inflammation and cognitive function in the U.S. geriatric population.
Novel serine/threonine-O-glycosylation with N-acetylneuraminic acid and 3-deoxy-D-manno-octulosonic acid by bacterial flagellin glycosyltransferases
Authors: Khairnar Aasawari , Sunsunwal Sonali , Babu Ponnusamy , Ramya T N C
Published: September 2020

Some bacterial flagellins are O-glycosylated on surface-exposed serine/threonine residues with nonulosonic acids such as pseudaminic acid, legionaminic acid and their derivatives by flagellin nonulosonic acid glycosyltransferases, also called motility-associated factors (Maf). We report here two new glycosidic linkages previously unknown in any organism, serine/threonine-O-linked N-acetylneuraminic acid (Ser/Thr-O-Neu5Ac) and serine/threonine-O-linked 3-deoxy-D-manno-octulosonic acid or keto-deoxyoctulosonate (Ser/Thr-O-KDO), both catalyzed by Geobacillus kaustophilus Maf and Clostridium botulinum Maf. We identified these novel glycosidic linkages in recombinant G. kaustophilus and C. botulinum flagellins that were coexpressed with their cognate recombinant Maf protein in Escherichia coli strains producing the appropriate nucleotide sugar glycosyl donor. Our finding that both G. kaustophilus Maf (putative flagellin sialyltransferase) and C. botulinum Maf (putative flagellin legionaminic acid transferase) catalyzed Neu5Ac and KDO transfer on to flagellin indicates that Maf glycosyltransferases display donor substrate promiscuity. Maf glycosyltransferases have the potential to radically expand the scope of neoglycopeptide synthesis and posttranslational protein engineering.
Team-based primary health care for non-communicable diseases: complexities in South India
Authors: Lall Dorothy , Engel Nora , Devadasan Narayanan , Horstman Klasien , Criel Bart
Published: September 2020

Chronic non-communicable diseases (NCDs), such as diabetes and cardiovascular diseases, have reached epidemic proportions worldwide. Health systems, especially those in low- and middle-income countries, such as India, struggle to deliver quality chronic care. A reorganization of healthcare service delivery is needed to strengthen care for chronic conditions. In this study, we evaluated the implementation of a package of tailored interventions to reorganize care, which were identified following a detailed analysis of gaps in delivering quality NCD care at the primary care level in India. Interventions included a redesign of the workflow at primary care clinics, a redistribution of tasks, the introduction of patient information records and the involvement of community health workers in the follow-up of patients with NCDs. An experimental case study design was chosen to study the implementation of the quality improvement measures. Three public primary care facilities in rural South India were selected. Qualitative methods were used to gain an in-depth understanding of the implementation process and outcomes of implementation. Observations, field notes and semi-structured interviews with staff at these facilities (n = 15) were thematically analysed to identify contextual factors that influenced implementation. Only one of the primary health centres implemented all components of the intervention by the end of 9 months. The main barriers to implementation were hierarchical arrangements that inhibited team-based care, the amount of time required for counselling and staff transfers. Team cohesion, additional staff and staff motivation seem to have facilitated implementation. This quality improvement research highlights the importance of building relational leadership to enable team-based care at primary care clinics in India. Redesigned organization of care and task redistribution is important solutions to deliver quality chronic care. However, implementing these will require capacity building of local primary care teams.
Diving into a Simple Anguilliform Swimmer’s Sensitivity
Authors: Battista Nicholas A
Published: September 2020

Synopsis

Computational models of aquatic locomotion range from modest individual simple swimmers in 2D to sophisticated 3D multi-swimmer models that attempt to parse collective behavioral dynamics. Each of these models contain a multitude of model input parameters to which its outputs are inherently dependent, that is, various performance metrics. In this work, the swimming performance’s sensitivity to parameters is investigated for an idealized, simple anguilliform swimming model in 2D. The swimmer considered here propagates forward by dynamically varying its body curvature, similar to motion of a Caenorhabditis elegans. The parameter sensitivities were explored with respect to the fluid scale (Reynolds number), stroke (undulation) frequency, as well as a kinematic parameter controlling the velocity and acceleration of each upstroke and downstroke. The input Reynolds number and stroke frequencies sampled were from [450, 2200] and [1, 3] Hz, respectively. In total, 5000 fluid–structure interaction simulations were performed, each with a unique parameter combination selected via a Sobol sequence, in order to conduct global sensitivity analysis. Results indicate that the swimmer’s performance is most sensitive to variations in its stroke frequency. Trends in swimming performance were discovered by projecting the performance data onto particular 2D subspaces. Pareto-like optimal fronts were identified. This work is a natural extension of the parameter explorations of the same model from Battista in 2020.
Sea-louse abundance on salmon farms in relation to parasite-control policy and climate change
Authors: Godwin Sean C , Krkosek Martin , Reynolds John D , Bateman Andrew W
Published: September 2020

The ectoparasitic copepods, sea lice (Lepeophtheirus salmonis and Caligus spp.), are major pests to salmon aquaculture and can also affect the health and survival of wild salmon. Policies exist to protect wild salmon by delousing farmed fish when louse abundance exceeds a threshold, but their effectiveness under future climate change is uncertain. We fitted a Bayesian model for sea-louse population dynamics and management to timeseries data of sea lice on farmed salmon in Pacific Canada and analysed the model under scenarios of warmer climates. We found that in high-temperature years, current parasite control policy becomes ineffective as sea-louse abundance is expected to increase. We simulated two alternative management scenarios and observed that both would decrease average louse counts on farms in high-temperature years relative to the current system but relied on more delousing treatments than are currently performed. We also found evidence that non-salmonids can play a role in louse transmission to farms, as increased farm colonization of Caligus clemensi occurs in April, coincident with wild herring (Clupea pallasii) spawner abundance. Our results highlight the need for careful management of sea lice on salmon farms in warmer years and the importance of policies designed to account for future environmental change.
Accounting for non-stationary stock–recruitment relationships in the development of MSY-based reference points
Authors: Zhang Fan , Regular Paul M , Wheeland Laura , Rideout Rick M , Morgan M Joanne
Published: September 2020

Asbtract

Stock–recruitment relationships (SRRs) may vary over time due to ecological and anthropogenic impacts, challenging traditional approaches of calculating maximum sustainable yield (MSY)-based reference points that assume constant population traits. We compare seven methods to calculate MSY, FMSY and BMSY by modelling constant, stochastic (uncorrelated), and autocorrelated SRRs using simulations and two case studies [Atlantic cod (Gadus morhua) and American plaice (Hippoglossoides platessoides) on the Grand Bank off Newfoundland, Canada]. Results indicated that the method used to model SRRs strongly affected the temporal pattern of recruitment projection, and the variations generated by autocorrelated SRRs were more similar to observed patterns. When the population productivity had low-frequency and large-magnitude variations, stochastic SRRs generated greater MSY and FMSY estimates than constant or autocorrelated SRRs, while no consistent pattern of BMSY was detected. In the case studies, stochastic and autocorrelated SRRs produced asymmetric relationships between fishing mortality and yield, with higher risk of overfishing by going beyond FMSY. Overall, our results suggest that caution should be taken when calculating MSY-based reference points in highly dynamic ecosystems, and correctly accounting for non-stationary population dynamics could, therefore, lead to more sustainable fisheries.
A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer
Authors: Franssen Linnea C , Chaplain Mark A J
Published: September 2020

Cancer invasion and metastatic spread to secondary sites in the body are facilitated by a complex interplay between cancer cells of different phenotypes and their microenvironment. A trade-off between the cancer cells’ ability to invade the tissue and to metastasize, and their ability to proliferate has been observed. This gives rise to the classification of cancer cells into those of mesenchymal and epithelial phenotype, respectively. Additionally, mixed phenotypic states between these two extremes exist. Cancer cells can transit between these states via epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). These processes are crucial for both the local tissue invasion and the metastatic spread of cancer cells. To shed light on the role of these phenotypic states and the transitions between them in the invasive and metastatic process, we extend our recently published multi-grid, hybrid, individual-based mathematical metastasis framework (Franssen et al. 2019, A mathematical framework for modelling the metastatic spread of cancer. Bull. Math. Biol., 81, 1965). In addition to cancer cells of epithelial and of mesenchymal phenotype, we now also include those of an intermediate partial-EMT phenotype. Furthermore, we allow for the switching between these phenotypic states via EMT and MET at the biologically appropriate steps of the invasion-metastasis cascade. We also account for the likelihood of spread of cancer cells to the various secondary sites and differentiate between the tissues of the organs involved in our simulations. Finally, we consider the maladaptation of metastasized cancer cells to the new tumour microenvironment at secondary sites as well as the immune response at these sites by accounting for cancer cell dormancy and death. This way, we create a first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade.
Progress and impact of 20 years of a lymphatic filariasis elimination programme in South-East Asia
Authors: Kapa D Ramaiah , Mohamed Ahmed Jamsheed
Published: September 2020

Background

The South-East Asia regional programme to eliminate lymphatic filariasis (LF) was launched in 2000. This study presents the progress and impact of the programme in the region.

Methods

Mass drug administration (MDA) and morbidity management data were accessed from the WHO preventive chemotherapy databank. The status of the programme in the nine South-East Asia countries was reviewed and progress was assessed. The impact of the programme on LF disease burden was estimated on the basis of the effectiveness of the MDA drugs against microfilaraemia and chronic disease.

Results

Under the MDA programme, 8.1 billion treatments were delivered in nine countries and 5.7 billion treatments were consumed by the target population during 2001–2018. Three of nine countries eliminated LF. Bangladesh is poised to reach its elimination goal by 2021. In the other five countries, 38–76% of intervention units completed intervention and surveillance is in progress. The MDA programme prevented or cured 74.9 million infections, equivalent to an 84.2% reduction. Close to 1 million lymphoedema patients and 0.5 million hydrocele patients were reported and are being provided with the minimum package of care.

Conclusions

The South-East Asia region's LF elimination programme reduced the burden of LF appreciably and is moving towards achieving the elimination goal in the next 8–10 y.
Physicians’ electronic inbox work patterns and factors associated with high inbox work duration
Authors: Akbar Fatema , Mark Gloria , Warton E. Margaret , Reed Mary E , Prausnitz Stephanie , East Jeffrey A , Moeller Mark F , Lieu Tracy A
Published: September 2020

Objectives

Electronic health record systems are increasingly used to send messages to physicians, but research on physicians’ inbox use patterns is limited. This study’s aims were to (1) quantify the time primary care physicians (PCPs) spend managing inboxes; (2) describe daily patterns of inbox use; (3) investigate which types of messages consume the most time; and (4) identify factors associated with inbox work duration.

Materials and Methods

We analyzed 1 month of electronic inbox data for 1275 PCPs in a large medical group and linked these data with physicians’ demographic data.

Results

PCPs spent an average of 52 minutes on inbox management on workdays, including 19 minutes (37%) outside work hours. Temporal patterns of electronic inbox use differed from other EHR functions such as charting. Patient-initiated messages (28%) and results (29%) accounted for the most inbox work time. PCPs with higher inbox work duration were more likely to be female (P < .001), have more patient encounters (P < .001), have older patients (P < .001), spend proportionally more time on patient messages (P < .001), and spend more time per message (P < .001). Compared with PCPs with the lowest duration of time on inbox work, PCPs with the highest duration had more message views per workday (200 vs 109; P < .001) and spent more time on the inbox outside work hours (30 minutes vs 9.7 minutes; P < .001).

Conclusions

Electronic inbox work by PCPs requires roughly an hour per workday, much of which occurs outside scheduled work hours. Interventions to assist PCPs in handling patient-initiated messages and results may help alleviate inbox workload.
Rapid Determination of Sufentanil in Human Plasma by UHPLC–QqQ-MS-MS
Authors: Zawadzki Marcin , Kowalski Grzegorz , Chłopaś-Konowałek Agnieszka , Siczek Marta , Sobieszczańska Małgorzata , Leppert Wojciech , Wieczorowska-Tobis Katarzyna , Szpot Paweł
Published: September 2020

This paper presents a rapid, sensitive and precise method developed and validated for the quantification of sufentanil in biological samples using ultra-performance liquid chromatography coupled with QqQ-MS-MS. Plasma samples were extracted with simple and fast liquid-liquid extraction (ethyl acetate, pH 9). Calibration curve showed linearity in the concentration range of 0.005–30 µg/L. The lower limit of quantification was 0.010 µg/L. The most important method features are low lower limit of quantification value, simple plasma extraction and small sample volume. This method is suitable not only for evaluation of the pharmacokinetics, toxicology, bioavailability and clinical pharmacology of sufentanil but also for the detection and identification of this compound in human plasma samples for forensic purposes.
Health equity considerations in COVID-19: geospatial network analysis of the COVID-19 outbreak in the migrant population in Singapore
Authors: Yi Huso , Ng Shu Tian , Farwin Aysha , Pei Ting Low Amanda , Chang Cheng Mun , Lim Jeremy
Published: September 2020

Background

Low-wage dormitory-dwelling migrant workers in Singapore were disproportionately affected by coronavirus disease 2019 (COVID-19) infection. This was attributed to communal living in high-density and unhygienic dormitory settings and a lack of inclusive protection systems. However, little is known about the roles of social and geospatial networks in COVID-19 transmission. The study examined the networks of non-work–related activities among migrant workers to inform the development of lockdown exit strategies and future pandemic preparedness.

Methods

A population-based survey was conducted with 509 migrant workers across the nation, and it assessed dormitory attributes, social ties, physical and mental health status, COVID-19-related variables and mobility patterns using a grid-based network questionnaire. Mobility paths from dormitories were presented based on purposes of visit. Two-mode social networks examined the structures and positions of networks between workers and visit areas with individual attributes.

Results

COVID-19 risk exposure was associated with the density of dormitory, social ties and visit areas. The migrant worker hub in the city centre was the most frequently visited for essential services of grocery shopping and remittance, followed by south central areas mainly for social gathering. The hub was positioned as the core with the highest degree of centrality with a cluster of workers exposed to COVID-19.

Conclusions

Social and geospatial networks of migrant workers should be considered in the implementation of lockdown exit strategies while addressing the improvement of living conditions and monitoring systems. Essential services, like remittance and grocery shopping at affordable prices, need to be provided near to dormitories to minimize excess gatherings.
Statistics and analysis of high-altitude wind above the western Tibetan Plateau
Authors: Qian Xuan , Yao Yongqiang , Wang Hongshuai , Zou Lei , Li Yao
Published: September 2020

This article aims at studying the characteristics of high-altitude wind at the Ali Observatory on the western Tibetan Plateau, as the high-altitude wind has been put forward as a critical parameter for site evaluation, especially for adaptive optics. We have run a meso-scale numerical weather research and forecasting (WRF) model in three nested domains with different horizontal resolutions, centred at the Ali Observatory; the model results with the highest horizontal resolution of 1 km and temporal resolution of 0.5 h are presented, and also statistical analyseis of vertical wind profiles and 200 hPa wind speed are performed. Moreover, comparisons of wind speeds obtained from model and radiosoundings are presented; as the vertical resolution has been proved to be key to the estimation of optical turbulence with meso-scale models, the vertical resolutions are both set to 50 m for wind profiles, which reveals a high level of agreement and provides a useful tool for site assessment. The results prove the good character of the high-altitude wind over the Ali region, especially in summer half year, with a yearly median 200 hPa wind speed of 33.6 m s−1 in 2016, and also provide proof of the potential advantage of the Ali Observatory for adaptive optics. Furthermore, we certify that meso-scale models can offer dependable estimation of high-altitude wind over the Tibetan Plateau; the wind simulations provided by the WRF model will be of great benefit for adaptive optics, which also provides the vertical distributions of CN2 and τ0 above astronomical observatories.
Stellar initial mass function variation in massive early-type galaxies: the potential role of the deuterium abundance
Authors: Davis Timothy A , van de Voort Freeke
Published: September 2020

The observed stellar initial mass function (IMF) appears to vary, becoming bottom-heavy in the centres of the most massive, metal-rich early-type galaxies. It is still unclear what physical processes might cause this IMF variation. In this paper, we demonstrate that the abundance of deuterium in the birth clouds of forming stars may be important in setting the IMF. We use models of disc accretion on to low-mass protostars to show that those forming from deuterium-poor gas are expected to have zero-age main-sequence masses significantly lower than those forming from primordial (high deuterium fraction) material. This deuterium abundance effect depends on stellar mass in our simple models, such that the resulting IMF would become bottom-heavy – as seen in observations. Stellar mass loss is entirely deuterium free and is important in fuelling star formation across cosmic time. Using the Evolution and Assembly of GaLaxies and their Environments (EAGLE) simulation we show that stellar mass-loss-induced deuterium variations are strongest in the same regions where IMF variations are observed: at the centres of the most massive, metal-rich, passive galaxies. While our analysis cannot prove that the deuterium abundance is the root cause of the observed IMF variation, it sets the stage for future theoretical and observational attempts to study this possibility.
μ⋆ masses: weak-lensing calibration of the Dark Energy Survey Year 1 redMaPPer clusters using stellar masses
Authors: Pereira M E S , Palmese A , Varga T N , McClintock T , Soares-Santos M , Burgad J , Annis J , Farahi A , Lin H , Choi A , DeRose J , Esteves J , Gatti M , Gruen D , Hartley W G , Hoyle B , Jeltema T , MacCrann N , Roodman A , Sánchez C , Shin T , von der Linden A , Zuntz J , Abbott T M C , Aguena M , Avila S , Bertin E , Bhargava S , Bridle S L , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , Desai S , Diehl H T , Dietrich J P , Doel P , Estrada J , Everett S , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , March M , Marshall J L , Melchior P , Menanteau F , Miquel R , Ogando R L C , Paz-Chinchón F , Plazas A A , Romer A K , Sanchez E , Scarpine V , Schubnell M , Serrano S , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarle G , Wechsler R H , Weller J , Zhang Y ,   (DES Collaboration)
Published: September 2020

We present the weak-lensing mass calibration of the stellar-mass-based μ⋆ mass proxy for redMaPPer galaxy clusters in the Dark Energy Survey Year 1. For the first time, we are able to perform a calibration of μ⋆ at high redshifts, z > 0.33. In a blinded analysis, we use ∼6000 clusters split into 12 subsets spanning the ranges 0.1 ≤ z < 0.65 and μ⋆ up to ${\sim} 5.5 \times 10^{13} \, \mathrm{M}_{\odot }$, and infer the average masses of these subsets through modelling of their stacked weak-lensing signal. In our model, we account for the following sources of systematic uncertainty: shear measurement and photometric redshift errors, miscentring, cluster-member contamination of the source sample, deviations from the Navarro–Frenk–White halo profile, halo triaxiality, and projection effects. We use the inferred masses to estimate the joint mass–μ⋆–z scaling relation given by $\langle M_{200c} | \mu _{\star },z \rangle = M_0 (\mu _{\star }/5.16\times 10^{12} \, \mathrm{M_{\odot }})^{F_{\mu _{\star }}} ((1+z)/1.35)^{G_z}$. We find $M_0= (1.14 \pm 0.07) \times 10^{14} \, \mathrm{M_{\odot }}$ with $F_{\mu _{\star }}= 0.76 \pm 0.06$ and Gz = −1.14 ± 0.37. We discuss the use of μ⋆ as a complementary mass proxy to the well-studied richness λ for: (i) exploring the regimes of low z, λ < 20 and high λ, z ∼ 1; and (ii) testing systematics such as projection effects for applications in cluster cosmology.
Gas-grain model of carbon fractionation in dense molecular clouds
Authors: Loison Jean-Christophe , Wakelam Valentine , Gratier Pierre , Hickson Kevin M
Published: September 2020

Carbon containing molecules in cold molecular clouds show various levels of isotopic fractionation through multiple observations. To understand such effects, we have developed a new gas-grain chemical model with updated 13C fractionation reactions (also including the corresponding reactions for 15 N, 18O, and 34S). For chemical ages typical of dense clouds, our nominal model leads to two 13C reservoirs: CO and the species that derive from CO, mainly s-CO and s-CH3OH, as well as C3 in the gas phase. The nominal model leads to strong enrichment in C3, c-C3H2, and C2H in contradiction with observations. When C3 reacts with oxygen atoms, the global agreement between the various observations and the simulations is rather good showing variable 13C fractionation levels that are specific to each species. Alternatively, hydrogen atom reactions lead to notable relative 13C fractionation effects for the two non-equivalent isotopologues of C2H, c-C3H2, and C2S. As there are several important fractionation reactions, some carbon bearing species are enriched in 13C, particularly CO, depleting atomic 13C in the gas phase. This induces a 13C depletion in CH4 formed on grain surfaces, an effect that is not observed in the CH4 in the Solar system, in particular on Titan. This seems to indicate a transformation of matter between the collapse of the molecular clouds, leading to the formation of the protostellar disc, and the formation of the planets. Or it means that the atomic carbon sticking to the grains reacts with the species already on the grains giving very little CH4.
Investigating the multiband non-thermal emission of the 100 TeV source eHWC J2019+368 with a pulsar wind nebula scenario
Authors: Fang Jun , Wen Lu , Yu Huan , Chen Songzhan
Published: September 2020

eHWC J2019+368 is one of the sources emitting γ-rays with energies higher than 100 TeV based on the recent measurement with the High Altitude Water Cherenkov Observatory (HAWC), and the origin is still in debate. The pulsar PSR J2021+3651 is spatially coincident with the TeV source. We investigate theoretically whether the multiband non-thermal emission of eHWC J2019+368 can originate from the pulsar wind nebula (PWN) G75.2+0.1 powered by PSR J2021+3651. In the model, the spin-down power of the pulsar is transferred to high-energy particles and magnetic field in the nebula. As the particles with an energy distribution of either a broken power law or a power law continually injected into the nebula, the multiband non-thermal emission is produced via synchrotron radiation and inverse Compton scattering. The spectral energy distribution of the nebula from the model with the reasonable parameters is generally consistent with the detected radio, X-ray, and TeV γ-ray fluxes. Our study supports that the PWN has the ability to produce the TeV γ-rays of eHWC J2019+368, and the most energetic particles in the nebula have energies up to about 0.4 PeV.