bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory Analysis of the Economically Justifiable Price of a Hypothetical RSV Vaccine for Older Adults in the Netherlands and the United Kingdom
Authors: Zeevat F , Luttjeboer J , Paulissen J H J , van der Schans J , Beutels P , Boersma C , Postma M J ,   RESCEU Investigators, Nair Harish , Campbell Harry , Openshaw Peter , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Kølsen Fischer Thea , van den Berge Maarten , Giaquinto Carlo , Kieffer Alexia , Demont Clarisse , Gallichan Scott , Dormitzer Philip , Leach Amanda , Dillon Laura , Aerssens Jeroen , Rosen Brian
Published: March 2021

Background

In older adults, the burden of respiratory syncytial virus (RSV) resembles that of influenza and may even be considered worse due to the lack of preventive interventions. This study was performed to identify the available literature on RSV infection in older adults, and to provide updated exploratory results of the cost-effectiveness of a hypothetical RSV vaccine in the Netherlands and the United Kingdom.

Methods

A literature search was performed in Medline and EMBASE on 11 November 2019, which served as input for a static decision-tree model that was used to estimate the EJP, for an RSV vaccine applying different willingness-to-pay (WTP) thresholds. WTP thresholds applied were €20 000 and €50 000 per quality-adjusted life-year for the Netherlands, and £20 000 and £30 000 per quality-adjusted life-year for the United Kingdom. Analyses were—in line with country-specific guidelines—conducted from a societal perspective for the Netherlands and a third-party payer perspective for the United Kingdom. The robustness of the cost-effectiveness results was tested in sensitivity analysis.

Results

After screening the literature, 3 studies for the Netherlands and 6 for the United Kingdom remained to populate the country-specific models. In the base case analysis for the Netherlands (mean RSV incidence, 3.32%), justifiable vaccine prices of €16.38 and €50.03 were found, based on applying the lower and higher WTP thresholds, respectively. Similarly, for the United Kingdom (mean incidence, 7.13%), vaccine prices of £72.29 and £109.74 were found, respectively.

Conclusion

RSV vaccination may well be cost-effective in both the Netherlands and the United Kingdom, depending on the exact RSV incidence, vaccine effectiveness and price. However, sensitivity analysis showed that the results were robust based on varying the different parameter estimates and assumptions. With RSV vaccines reaching the final stages of development, a strong need exists for cost-effectiveness studies to understand economically justifiable pricing of the vaccine.
Lack of Detection of Haemophilus influenzae Using Adult Blood Culture Bottles Inoculated at Low Volumes
Authors: Freeman Tanner J , Krenke Charlene , Mitchell Stephanie L
Published: March 2021

Background

Based on guidelines from the Infectious Diseases Society of America and the American Society for Microbiology, many pediatric hospitals are implementing weight-based collection guidelines for blood cultures. To simplify the process of culture collection, there has been interest in validating the use of adult blood culture bottles with low volumes, which may allow for a “one size fits all” bottle.

Method

This study examined 9 clinically relevant organisms (Staphylococcus aureus, Streptococcus pneumonia, Streptococcus agalactiae, Enterococcus faecium, Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, Candida glabrata, and Candida albicans) utilizing the BD BacTec system at various inoculation volumes and dilutions to assess performance, based on time to positivity, of adult blood culture bottles compared with pediatric blood culture bottles.

Results

There was a lack of detection of H. influenzae using adult blood culture bottles inoculated at low volumes, whereas pediatric bottles detected H. influenzae regardless of dilution–volume combinations tested.

Conclusions

Exclusive use of adult blood culture bottles may not detect H. influenzae bacteremia in the setting of low-volume inoculum.
Scientific and Legal Mechanisms for Addressing Model Uncertainties: Negotiating the Right Balance in Finnish Judicial Review?
Authors: Paloniitty Tiina , Kotamäki Niina
Published: March 2021

Environmental models are ubiquitous in assessing the environmental impacts of planned projects. Modelling is an inferential process and includes various mechanisms to address the uncertainty of the outcome. In this article, we acknowledge the continuum of uncertainty assessments and identify the legal mechanisms with which Finnish judicial review—characterised by broad scope of review and in-house expert judges—has encountered model uncertainty. Closely examining 10 waters-related cases heard by the Supreme Administrative Court of Finland, we explain the porous yet substantial boundary between science and law revealed by the cases. The cases demonstrate the elegance with which courts can strike a balance between the contingent precautionary principle, gradually decreasing scientific uncertainty, and the procedural constraints under which they operate. We conclude by analysing the traces towards reciprocality and adaptivity the cases reveal, encouraged by the iterative modelling mechanism and challenged by the constitutional restrictions on the scope of review.
Populism and Securitization: The Corrosion of Elite Security Authority in a US–Mexico Border State
Authors: Slaven Mike
Published: March 2021

Populists have often seemed influential in the securitization of migration, in great part through pressuring non-populist governing elites into “mainstreaming” more hardline immigration positions. This article asks why, given the presumption in securitization literatures that elite insiders possess strong authority in defining security, non-populist governing elites often in fact cede ground to populist challengers who paint immigration as a threat. Securitization and political science literatures paint very different pictures of elite–challenger dynamics, but populist and securitization claims possess key ideational similarities, in relation to the holism and autonomy of the political community, and the apoliticism of pursuing purportedly self-evident goals. However, populism articulates securitarian concepts through a moralized anti-elitism that impugns elite authority, portraying governing elites as corruptly inert toward threats facing “the people.” This article explores how this ideational relationship may affect securitization processes through a process-tracing study of the populist radical right's successful pressuring of governing elites to securitize migration in the US state of Arizona. There, populists’ moralized accusations of corrupt elite inaction toward urgent security threats moved governing elites to adopt positions intended to demonstrate responsiveness to public border-security anxieties, thereby inscribing securitization. Taking an “ideational” view of both concepts shows how they can form a politically influential account of “common sense.” By undermining elite security authority—thus inverting the typically theorized power dynamics of securitization—populism may open new pathways for securitized policies to emerge.
Papain-like cysteine proteases are required for the regulation of photosynthetic gene expression and acclimation to high light stress
Authors: Alomrani Sarah , Kunert Karl J , Foyer Christine H
Published: March 2021

Chloroplasts are considered to be devoid of cysteine proteases. Using transgenic Arabidopsis lines expressing the rice cystatin, oryzacystatin I (OC-I), in the chloroplasts (PC lines) or cytosol (CYS lines), we explored the hypothesis that cysteine proteases regulate photosynthesis. The CYS and PC lines flowered later than the wild type (WT) and accumulated more biomass after flowering. In contrast to the PC rosettes, which accumulated more leaf chlorophyll and carotenoid pigments than the WT, the CYS lines had lower amounts of leaf pigments. High-light-dependent decreases in photosynthetic carbon assimilation and the abundance of the Rubisco large subunit protein, the D1 protein, and the phosphorylated form of D1 proteins were attenuated in the CYS lines and reversed in the PC lines relative to the WT. However, the transgenic lines had higher amounts of LHC, rbcs, pasbA, and pasbD transcripts than the WT, and also showed modified chloroplast to nucleus signalling. We conclude that cysteine proteases accelerate the reconfiguration of the chloroplast proteome after flowering and in response to high-light stress. Inhibition of cysteine proteases, such as AtCEP1, slows chloroplast protein degradation and stimulates photosynthetic gene expression and chloroplast to nucleus signalling, enhancing stress tolerance traits.
Use of Sundt Clip Graft for the Treatment of Intracranial Aneurysms: 2-Dimensional Operative Video
Authors: Rinaldo Lorenzo , Meyer Fredric B , Van Gompel Jamie J
Published: March 2021

Dr Thoralf Sundt III joined the department of neurosurgery at Mayo Clinic in 1969 and served as chairman from 1980 until his death in 1992. Dr Sundt was a pioneer in the field of cerebrovascular neurosurgery and among his many contributions to neurosurgical technology was the introduction of the Sundt clip graft (Codman, Raynham, Massachusetts), which was developed in partnership with Dr George Kees. This device is a vessel-encircling Teflon or Dacron graft loaded on a circular metallic spring initially designed to repair injuries to vessel walls during intracranial aneurysm surgery,
1
which was not an uncommon complication resulting from the use of contemporary aneurysm clips.
2
When used for this purpose, the clip graft has demonstrated both safety and efficacy in a modern series of surgical treatment of intracranial aneurysm.
3
An additional application of the clip graft is the direct clipping of aneurysms, particularly side-wall aneurysms, though Dr Sundt recognized that the potential to occlude perforating arteries adjacent to the aneurysm neck would limit the general use of the clip graft for aneurysm clipping.
2
In the following video, we present archival footage of Dr Sundt utilizing the Sundt clip graft during intracranial aneurysm surgery. The 3 cases are of the treatment of posterior communicating, middle cerebral, and anterior communicating artery aneurysms and depict the potential applications of the clip graft during aneurysm surgery. We also present footage of animal experiments Dr Sundt performed to validate the use of the clip graft. This footage likely represents some of the first microscopic neurosurgical recordings ever made.

The patients consented to the procedure and to presentation of video recordings at the time of initial surgery.

Image of Sundt at 0:11, Reproduced with permission from the American Association of Neurological Surgeons, 5550 Meadowbrook Dr, Rolling Meadows, IL 60008. Figures at 2:26 and 2:28, from Park PJ, Meyer FB, The Sundt clip graft, Neurosurgery, 2010;66(6 suppl operative):300-305, by permission of the Congress of Neurological Surgeons. Figure at 2:35, ©2009 Mayo, Clingman. Used with permission.
Microscopic coupled-channel calculation of proton and alpha inelastic scattering to the $4^+_1$ and $4^+_2$ states of $^{24}\textrm{Mg}$
Authors: Kanada-En’yo Yoshiko , Ogata Kazuyuki
Published: March 2021

The triaxial and hexadecapole deformations of the $K^\pi=0^+$ and $K^\pi=2^+$ bands of $^{24}$Mg have been investigated by the inelastic scatterings of various probes, including electrons, protons, and alpha($\alpha$) particles, for a prolonged time. However, it has been challenging to explain the unique properties of the scatterings observed for the $4^+_1$ state through reaction calculations. This paper investigates the structure and transition properties of the $K^\pi=0^+$ and $K^\pi=2^+$ bands of $^{24}$Mg employing the microscopic structure and reaction calculations via inelastic proton and $\alpha$ scattering. In particular, the $E4$ transitions to the $4^+_1$ and $4^+_2$ states are reexamined. The structure of $^{24}$Mg was calculated employing the variation after the parity and total angular momentum projections in the framework of the antisymmetrized molecular dynamics (AMD). The inelastic proton and $\alpha$ reactions were calculated by the microscopic coupled-channel (MCC) approach by folding the Melbourne $g$-matrix $NN$ interaction with the AMD densities of $^{24}$Mg. Reasonable results were obtained on the properties of the structure, including the energy spectra and $E2$ and $E4$ transitions of the $K^\pi=0^+$ and $K^\pi=2^+$ bands owing to the enhanced collectivity of triaxial deformation. The MCC+AMD calculation successfully reproduced the angular distributions of the $4^+_1$ and $4^+_2$ cross sections of proton scattering at incident energies of $E_p=40$–100 MeV and $\alpha$ scattering at $E_\alpha=100$–400 MeV. This is the first microscopic calculation to describe the unique properties of the $0^+_1\to 4^+_1$ transition. In the inelastic scattering to the $4^+_1$ state, the dominant two-step process of the $0^+_1\to 2^+_1\to 4^+_1$ transitions and the deconstructive interference in the weak one-step process were essential.
Exploratory Analysis of Physical Therapy Process of Care and Psychosocial Impact of the COVID-19 Pandemic on Physical Therapists
Authors: Tiwari Devashish , Naidoo Keshrie , Chatiwala Naseem , Bartlo Pamela L , Triola Allison , Ong Brandon , Gore Shweta
Published: March 2021

Objective

The purpose of this study was to investigate the physical therapy process of care, clinical practices, and the self-reported psychosocial impact of working during the 2020 pandemic on physical therapists and physical therapist assistants.

Methods

An electronic survey including closed and open-ended questions was distributed to physical therapists employed in a range of health care settings across the United States.

Results

Physical therapy use and process of care varied across settings. Feasibility of performing an assessment was the main driver for selection of outcome measures. Interventions were mainly geared toward improving respiratory function and deconditioning. Prone patient positioning, now commonplace, was used infrequently by therapists in acute care prior to coronavirus disease 2019 (COVID-19). Similarly, outpatient and home care settings noted an increase in the use of respiratory-driven interventions such as incentive spirometry and breathing exercises. Qualitative data analysis revealed both physical barriers (personal protective equipment [PPE]) and social barriers to care. Therapists noted challenges in discharge planning and patient/family education due to the impact of social isolation. They also noted difficulty maintaining productivity standards because of additional time spent in changing PPE and following safety measures. Participants dealt with rapid changes in their role, changing productivity standards, and needing to increase their knowledge in a short amount of time.

Conclusion

Physical therapy use varied widely across settings. Despite some concern for personal health, respondents felt that the COVID-19 pandemic increased a sense of togetherness among team members and promoted greater appreciation for life and work.

Impact

This exploration of the process of care and current clinical practices across settings provides important knowledge about the role of physical therapists and physical therapist assistants in the care of patients with COVID-19. Gaining an understanding of the psychosocial impact of the pandemic among therapists could assist in creating solutions to better support clinicians’ well-being.
Mask is a must: the need of protection and safety against COVID-19
Authors: Punsalan Mairre Louie D , Salunga Angelyn T
Published: March 2021

As the strict quarantine measures ease and the availability of vaccines, reports have proposed that people of varying ages are now less likely to wear mask despite its added protection and safety against COVID-19. In a recent short article published, it was found out that older age groups may less likely to wear face masks in comparison with the younger ones. The importance of face masks must always be geared toward better health outcomes and safety precautions of wearing face mask as the world battles with the pandemic. With varying studies, face mask can be an essential means to mitigate the spread of COVID-19.
Genome Sequence of Rhizoctonia solani Anastomosis Group 4 Strain Rhs4ca, a Widespread Pathomycete in Field Crops
Authors: Zhang Zhengkun , Xia Xinyao , Du Qian , Xia Lei , Ma Xiaoyu , Li Qiyun , Liu Wende
Published: March 2021

Rhizoctonia solani is an important soil-borne fungal pathogen that causes serious diseases on many agricultural crops and vegetables. Here, we report a complete genome assembly of R. solani AG4 (assembly: 45.47 Mb; contig N50: 1.56 Mb), using a combination of Illumina paired-end and PacBio long-read sequencing data. A total of 267 noncoding RNAs and 11,592 genes were predicted, including 109 genes associated with carbohydrate-active enzymes and 2,488 genes involved in host-pathogen interactions. The complete genome of R. solani AG4 represents a valuable base for studying interactions between host plants and pathogenic fungi and to search for potential antimicrobial targets.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Environmental hazards, social inequality, and fetal loss: Implications of live-birth bias for estimation of disparities in birth outcomes
Authors: Goin Dana E. , Casey Joan A. , Kioumourtzoglou Marianthi-Anna , Cushing Lara J. , Morello-Frosch Rachel
Published: March 2021

Background:

Restricting to live births can induce bias in studies of pregnancy and developmental outcomes, but whether this live-birth bias results in underestimating disparities is unknown. Bias may arise from collider stratification due to an unmeasured common cause of fetal loss and the outcome of interest, or depletion of susceptibles, where exposure differentially causes fetal loss among those with underlying susceptibility.

Methods:

We conducted a simulation study to examine the magnitude of live-birth bias in a population parameterized to resemble one year of conceptions in California (N = 625,000). We simulated exposure to a non–time-varying environmental hazard, risk of spontaneous abortion, and time to live birth using 1000 Monte Carlo simulations. Our outcome of interest was preterm birth. We included a social vulnerability factor to represent social disadvantage, and estimated overall risk differences for exposure and preterm birth using linear probability models and stratified by the social vulnerability factor. We calculated how often confidence intervals included the true point estimate (CI coverage probabilities) to illustrate whether effect estimates differed qualitatively from the truth.

Results:

Depletion of susceptibles resulted in a larger magnitude of bias compared with collider stratification, with larger bias among the socially vulnerable group. Coverage probabilities were not adversely affected by bias due to collider stratification. Depletion of susceptibles reduced coverage, especially among the socially vulnerable (coverage among socially vulnerable = 46%, coverage among nonsocially vulnerable = 91% in the most extreme scenario).

Conclusions:

In simulations, hazardous environmental exposures induced live-birth bias and the bias was larger for socially vulnerable women.
Mass Incarceration and Children's Health
Authors: Conway James M.
Published: March 2021

Children's health indicators such as mortality and adverse birth outcomes are poorer in the United States than in comparable nations. These measures also show racial inequities within the United States, with Black children experiencing the highest levels. Mass incarceration may partially explain these findings. High incarceration rates can disrupt community functioning, influencing behavior and health. The purpose of the current study was to conduct a macro (state)-level analysis examining whether yearly state incarceration rates predict health outcomes including infant, child, and teen mortality as well as preterm birth and low birth weight. It was hypothesized that prior year incarceration rates would show positive relationships with all outcomes and that relationships would be stronger for Black than for white children. Yearly state-level panel data were gathered from 1990 to 2017. Weighted least squares regression used states' prior year incarceration rates to predict child health outcomes, using controls for overall state effects and year-to-year effects. Time-varying covariates such as state unemployment rate were also included to address the possibility of spurious relationships. Results indicated that as hypothesized, incarceration rates positively predicted infant mortality, child mortality (for Black children only), preterm births, and low-weight births. Relationships tended to be stronger for Black than for white children.
Effect of Workstation Type on the Relationship Between Fatigue, Physical Activity, Stress, and Sleep
Authors: Goel Rahul , Pham Alan , Nguyen Hung , Lindberg Casey , Gilligan Brian , Mehl Matthias R. , Heerwagen Judith , Kampschroer Kevin , Sternberg Esther M. , Najafi Bijan
Published: March 2021

Objective:

This study examined office workstation types’ impact on the relationship between fatigue and three health metrics: physical activity, stress, and sleep quality.

Methods:

Data from 225 office workers were collected for perceived fatigue, perceived sleep quality (Pittsburgh Sleep Quality Index [PSQI]), physiological stress response (standard deviation of heart rate variability [HRV]), and physical activity (total activity in minutes) during three consecutive workdays. Stress and physical activity were measured using chest-worn sensors. Workers were then categorized as tired or not-tired based on the median of the fatigue rating.

Results:

Among tired workers, open-bench seating workers had increased physical activity, improved sleep quality, and reduced stress compared with workers in private offices and cubicles.

Conclusions:

Office workstation types influence physical activity and levels of stress during work hours, which in turn affect sleep quality.
It Depends
Authors: Bourgault Annette M. , Penoyer Daleen A. , Upvall Michele J.
Published: March 2021

Short peripheral catheters (SPCs) are frequently idle when they are not being used for clinical indications. Focus group interviews were performed with multidisciplinary clinicians at a large tertiary hospital to explore SPC practice related to inserting or maintaining idle SPCs. Findings indicated that decision-making regarding insertion and removal of peripheral intravenous catheters depends on internal and external influences, such as the clinicians' knowledge and skills, emotional responses, expectations of others, organizational policies and practices, and the patient. In today's complex health care environment, the need for an SPC may constantly change, yet decision-making about SPC insertion and removal must remain patient-centered and evidence-based.
Administration of 3% Sodium Chloride Via a Peripheral Vein
Authors: Metheny Norma A. , Moritz Michael L.
Published: March 2021

Three percent sodium chloride (3% NaCl) is a hyperosmolar agent that can be lifesaving for patients with severe hyponatremic encephalopathy, traumatic brain injury, and cerebral edema. Until recently, many institutions restricted the infusion of 3% NaCl to a central venous site to avoid infusion related adverse events (IRAEs) in peripheral veins. A growing number of studies have reported relatively safe administration of 3% NaCl through a peripheral vein. The incidences of IRAEs were evaluated in 9 studies that included 837 patients who received 3% NaCl through a peripheral vein. Infusion reactions were either uncommon or no more frequent than with routine solutions. The authors provide guidelines for the administration of and monitoring for complications associated with 3% NaCl through a peripheral vein, discuss the management of symptomatic hyponatremia, and provide illustrative cases.
A Novel Fast CT Perfusion Core-Penumbra Mismatch Score
Authors: Pozzi-Mucelli Roberta A. , Furlanis Giovanni , Caruso Paola , Lugnan Carlo , Zdjelar Adrian , Degrassi Ferruccio , Bottaro Lorella , Ukmar Maja , Naccarato Marcello , Manganotti Paolo , Cova Maria A.
Published: March 2021

Background:

Advanced neuroimaging can identify patients who can most benefit from reperfusion treatment, discriminating between ischemic core and penumbra area in a quick and accurate manner. Despite core-penumbra mismatch being an independent prognostic factor, computed tomography perfusion (CTP) assessment is still debated in hyperacute decision-making. The authors aimed to study a novel CTP mismatch score in emergency settings and to investigate its relation with clinical outcome in acute ischemic stroke patients treated with intravenous thrombolysis (IVT).

Methods:

Neuroimaging and clinical data of 226 consecutive acute ischemic stroke patients were analyzed. The study population was divided into 5 different CTP scores: (0) without perfusion deficit, (1) only penumbra, (2) penumbra > core, (3) core ≥ penumbra, (4) only core. For differences in outcome between treated and nontreated patients, and among CTP core-penumbra groups to be assessed, the authors have evaluated the outcome in terms of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at discharge and symptomatic intracerebral hemorrhage.

Results:

A decrease in NIHSS was statistically greater in IVT-treated patients compared to nontreated patients showing only penumbra (ΔNIHSS%: 80.0% vs. 50.0%; P=0.0023) or no perfusion deficit (ΔNIHSS%: 89.4% vs. 61.5%; P=0.027) on CTP maps. The same trend was found in other groups without significant difference. A significant correlation was found in IVT patients between core/penumbra score and outcome in terms of ΔNIHSS (Kendall τ=−0.19; P=0.004).

Conclusions:

The authors proposed a novel immediate CTP assessment to score perfusion mismatch in emergency settings to guide clinicians’ decision-making for aggressive treatment and to prevent stroke-related disability.
Scaling and responses of extreme hourly precipitation in three climate experiments with a convection-permitting model
Authors: Lenderink Geert , de Vries Hylke , Fowler Hayley J. , Barbero Renaud , van Ulft Bert , van Meijgaard Erik
Published: March 2021

It is widely recognized that future rainfall extremes will intensify. This expectation is tied to the Clausius-Clapeyron (CC) relation, stating that the maximum water vapour content in the atmosphere increases by 6–7% per degree warming. Scaling rates for the dependency of hourly precipitation extremes on near-surface (dew point) temperature derived from day-to-day variability have been found to exceed this relation (super-CC). However, both the applicability of this approach in a long-term climate change context, and the physical realism of super-CC rates have been questioned. Here, we analyse three different climate change experiments with a convection-permitting model over Western Europe: simple uniform-warming, 11-year pseudo-global warming and 11-year global climate model driven. The uniform-warming experiment results in consistent increases to the intensity of hourly rainfall extremes of approximately 11% per degree for moderate to high extremes. The other two, more realistic, experiments show smaller increases—usually at or below the CC rate—for moderate extremes, mostly resulting from significant decreases to rainfall occurrence. However, changes to the most extreme events are broadly consistent with 1.5–2 times the CC rate (10–14% per degree), as predicted from the present-day scaling rate for the highest percentiles. This result has important implications for climate adaptation.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Sensitivity of organized convective storms to model grid spacing in current and future climates
Authors: Prein A. F. , Rasmussen R. M. , Wang D. , Giangrande S. E.
Published: March 2021

Mesoscale convective systems (MCSs) are complexes of thunderstorms that become organized and cover hundreds of kilometres over several hours. MCSs are prolific rain producers in the tropics and mid-latitudes and are the major cause of warm-season flooding. Traditionally, climate models have difficulties in simulating MCSs partly due to the misrepresentation of complex process interactions that operate across a large range of scales. Significant improvements in simulating MCSs have been found in kilometre-scale models that explicitly simulate deep convection. However, these models operate in the grey zone of turbulent motion and have known deficiencies in simulating small-scale processes (e.g. entrainment, vertical mass transport). Here, we perform mid-latitude idealized ensemble MCS simulations under current and future climate conditions in three atmospheric regimes: hydrostatic (12 km horizontal grid spacing; Δx), non-hydrostatic (Δx = 4, 2 and 1 km) and large eddy scale (Δx = 500 m and 250 m). Our results show a dramatic improvement in simulating MCS precipitation, movement, cold pools, and cloud properties when transitioning from 12 km to 4 km Δx. Decreasing Δxbeyond 4 km results in modest improvements except for up- and downdraft sizes, average vertical mass fluxes, and cloud top height and temperature, which continue to change. Most important for climate modelling is that Δx = 4 km simulations reliably capture most MCS climate change signals compared to those of the Δx = 250 m runs. Significantly different climate change signals are found in Δx = 12 km runs that overestimate extreme precipitation changes by up to 100%.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Challenges and outlook for convection-permitting climate modelling
Authors: Kendon E. J. , Prein A. F. , Senior C. A. , Stirling A.
Published: March 2021

Climate projections at very high resolution (kilometre-scale grid spacing) are becoming affordable. These ‘convection-permitting’ models (CPMs), commonly used for weather forecasting, better represent land-surface characteristics and small-scale processes in the atmosphere such as convection. They provide a step change in our understanding of future changes at local scales and for extreme weather events. For short-duration precipitation extremes, this includes capturing local storm feedbacks, which may modify future increases. Despite the major advance CPMs offer, there are still key challenges and outstanding science issues. Heavy rainfall tends to be too intense; there are challenges in representing land-surface processes; sub-kilometre scale processes still need to be parametrized, with existing parametrization schemes often requiring development for use in CPMs; CPMs rely on the quality of lateral boundary forcing and typically do not include ocean-coupling; large CPM ensembles that comprehensively sample future uncertainties are costly. Significant progress is expected over the next few years: scale-aware schemes may improve the representation of unresolved convective updrafts; work is underway to improve the modelling of complex land-surface fluxes; CPM ensemble experiments are underway and methods to synthesize this information with larger coarser-resolution model ensembles will lead to local-scale predictions with more comprehensive uncertainty context for user application. Large-domain (continental or tropics-wide) CPM climate simulations, potentially with additional earth-system processes such as ocean and wave coupling and terrestrial hydrology, are an exciting prospect, allowing not just improved representation of local processes but also of remote teleconnections.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Incorporating climate change in flood estimation guidance
Authors: Wasko Conrad , Westra Seth , Nathan Rory , Orr Harriet G. , Villarini Gabriele , Villalobos Herrera Roberto , Fowler Hayley J.
Published: March 2021

Research into potential implications of climate change on flood hazard has made significant progress over the past decade, yet efforts to translate this research into practical guidance for flood estimation remain in their infancy. In this commentary, we address the question: how best can practical flood guidance be modified to incorporate the additional uncertainty due to climate change? We begin by summarizing the physical causes of changes in flooding and then discuss common methods of design flood estimation in the context of uncertainty. We find that although climate science operates across aleatory, epistemic and deep uncertainty, engineering practitioners generally only address aleatory uncertainty associated with natural variability through standards-based approaches. A review of existing literature and flood guidance reveals that although research efforts in hydrology do not always reflect the methods used in flood estimation, significant progress has been made with many jurisdictions around the world now incorporating climate change in their flood guidance. We conclude that the deep uncertainty that climate change brings signals a need to shift towards more flexible design and planning approaches, and future research effort should focus on providing information that supports the range of flood estimation methods used in practice.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks'.
Managing the effects of extreme sub-daily rainfall and flash floods—a practitioner's perspective
Authors: Dale Murray
Published: March 2021

Extreme sub-daily rainfall affects flooding in the UK and urban pollution management. Water utilities in the UK need to understand the characteristics of this rainfall, and how it may change in the future in order to plan for and manage these impacts. There is also significant interest from infrastructure owners and urban authorities exposed to flood risk from short-period, intense rainfall events. This paper describes how UK flood risk guidance incorporates allowances for climate change and how recent research using convection-permitting climate models is helping to inform this guidance. The guidance documents are used by engineers and scientists in the modelling of sewer networks, smaller river catchments and urban drainage areas and provide values to ‘uplift' rainfall event data used as model inputs to reflect climate change model projections. With an increasing focus on continuous simulation modelling using time series rainfall, research into adjusting time series data to reflect future rainfall characteristics in convection-permitting climate models is discussed. Other knowledge gaps for practitioners discussed are the potential changing shape (profile) of future rainfall events and future changes in antecedent wetness conditions. The author explains the challenge of developing simple and effective guidance for practitioners from the complex scientific output.

This article is part of a discussion meeting issue ‘Intensification of short-duration rainfall extremes and implications for flash flood risks’.
Mycolicibacterium nivoides sp. nov isolated from a peat bog
Authors: Dahl John L. , Gatlin III Wayne , Tran Phuong M. , Sheik Cody S.
Published: March 2021

A fast-growing, non-chromogenic, acid-fast-staining bacterium (DL90T) was isolated from a peat bog in northern Minnesota. On the basis of 16S rRNA gene sequence similarity (99.8 % identity with

Mycolicibacterium septicum

and 98 % with

Mycolicibacterium peregrinum

) and chemotaxonomic data (fatty acid content), strain DL90T represents a member of the genus

Mycolicibacterium

. Physiological tests (growth curves, biofilm formation, antibiotic sensitivity, colony morphologies and heat tolerance) and biochemical analysis (arylsulfatase activity and fatty acid profiles) distinguish DL90T from its closest relative

M. septicum

. Phylogenomic reconstruction of the ‘Fortuitium–Vaccae’ clade, digital DNA–DNA hybridization (DDH) values of 61 %, and average nucleotide identity (ANI) values of approximately 95 % indicate that DL90T is likely to be diverged from

M. septicum

. Thus, we propose that DL90T represents a novel species, given the name Mycolicibacterium nivoides with the type strain being isolate DL90T (=JCM 32796T=NCCB 100660T).
Trade-offs between individual and ensemble forecasts of an emerging infectious disease
Authors: Oidtman Rachel J. , Omodei Elisa , Kraemer Moritz U. G. , Castañeda-Orjuela Carlos A. , Cruz-Rivera Erica , Misnaza-Castrillón Sandra , Cifuentes Myriam Patricia , Rincon Luz Emilse , Cañon Viviana , de Alarcon Pedro , España Guido , Huber John H. , Hill Sarah C. , Barker Christopher M. , Johansson Michael A. , Manore Carrie A. , Reiner Robert C. , Rodriguez-Barraquer Isabel , Siraj Amir S. , Frias-Martinez Enrique , García-Herranz Manuel , Perkins T. Alex
Published: March 2021

When new pathogens emerge, numerous questions arise about their future spread, some of which can be addressed with probabilistic forecasts. The many uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among model structures and assumptions, however. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance of a suite of 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about the role of human mobility in driving transmission, spatiotemporal variation in transmission potential, and the number of times the virus was introduced. All models used the same core transmission model and the same iterative data assimilation algorithm to generate forecasts. By assessing forecast performance through time using logarithmic scoring with ensemble weighting, we found that which model assumptions had the most ensemble weight changed through time. In particular, spatially coupled models had higher ensemble weights in the early and late phases of the epidemic, whereas non-spatial models had higher ensemble weights at the peak of the epidemic. We compared forecast performance of the equally weighted ensemble model to each individual model and identified a trade-off whereby certain individual models outperformed the ensemble model early in the epidemic but the ensemble model outperformed all individual models on average. On balance, our results suggest that suites of models that span uncertainty across alternative assumptions are necessary to obtain robust forecasts in the context of emerging infectious diseases.
Seroepidemiology of SARS-CoV-2 infections in an urban Nicaraguan population
Authors: González Fredman , Vielot Nadja A. , Sciaudone Michael , Toval-Ruíz Christian , Premkumar Lakshmanane , Gutierrez Lester , Cuadra Edwing Centeno , Blandón Patricia , Silva Aravinda M. de , Rubinstein Rebecca , Bowman Natalie , Becker-Dreps Sylvia , Bucardo Filemon
Published: March 2021

In a Nicaraguan population-based cohort, SARS-CoV-2 seroprevalence was 34%, with higher prevalence in children compared to adults. Having a seropositive household member was associated with a two-fold probability of individual seropositivity, suggesting a role for household transmission. Co-morbidities and preventive behaviors were not associated with SARS-CoV-2 seroprevalence.
SARS-CoV-2 Total and Subgenomic RNA Viral Load in Hospitalized Patients
Authors: Dimcheff Derek E. , Valesano Andrew L. , Rumfelt Kalee E. , Fitzsimmons William J. , Blair Christopher , Mirabelli Carmen , Petrie Joshua G. , Martin Emily T. , Bhambhani Chandan , Tewari Muneesh , Lauring Adam S.
Published: March 2021

Understanding viral load in patients infected with SARS-CoV-2 is critical to epidemiology and infection control. Previous studies have demonstrated that SARS-CoV-2 RNA can be detected for many weeks after symptom onset. The clinical significance of this finding is unclear and, in most patients, likely does not represent active infection. There are, however, patients who shed infectious virus for weeks. Detection of subgenomic RNA transcripts expressed by SARS-CoV-2 has been proposed to represent productive infection and may be a tractable marker for monitoring infectivity. Here, we use RT-PCR to quantify total and subgenomic nucleocapsid (N) and envelope (E) transcripts in 190 SARS-CoV-2 positive samples collected on hospital admission. We relate these findings to duration of symptoms. We find that all transcripts decline at the same rate; however, subgenomic E becomes undetectable before other transcripts. In Kaplan-Meier analysis the median duration of symptoms to a negative test is 14 days for sgE and 25 days for sgN. There is a linear decline in subgenomic RNA compared to total RNA suggesting subgenomic transcript copy number is highly dependent on copy number of total transcripts. The mean difference between total N and subgenomic N is 16-fold (4.0 cycles) and the mean difference between total E and sub-genomic E is 137-fold (7.1 cycles). This relationship is constant over duration of symptoms allowing prediction of subgenomic copy number from total copy number. Although Subgenomic E is undetectable at a time that may more closely reflect the duration of infectivity, its utility in determining active infection may be no more useful than a copy number threshold determined for total transcripts.
Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults
Authors: Formica Neil , Mallory Raburn , Albert Gary , Robinson Michelle , Plested Joyce S. , Cho Iksung , Robertson Andreana , Dubovsky Filip , Glenn Gregory M. ,   for the 2019nCoV-101 Study Group
Published: March 2021

Background

NVX-CoV2373 is a recombinant severe acute respiratory coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.

Methods

The phase 2 component of our randomized, placebo-controlled, phase 1-2 trial was designed to identify which dosing regimen of NVX-CoV2373 should move forward into late phase studies in younger (18-59 years) and older (60-84 years) participants and was based on immunogenicity and safety data through day 35 (14 days after the second dose). Participants were randomly assigned to receive either one or two intramuscular doses of 5-µg or 25-µg NVX-CoV2373 or placebo, 21 days apart. Primary endpoints were immunoglobulin G (IgG) anti-spike protein response, 7-day solicited reactogenicity, and unsolicited adverse events. A key secondary endpoint was wild-type virus neutralizing antibody response.

Results

After randomization, approximately 250 participants each were assigned to one of four vaccine groups or placebo. Of these, approximately 45% were older participants. Reactogenicity was predominantly mild to moderate in severity and of short duration (median <3 days) after first and second vaccination with NVX-CoV2373, with higher frequencies and intensity after second vaccination and with the higher dose, and occurred less frequently and was of lower intensity in older participants. The two-dose regimen of 5-µg NVX-CoV2373 induced robust geometric mean titer (GMT) IgG anti-spike protein (65,019 and 28,137 EU/mL) and wild-type virus neutralizing antibody (2201 and 981 titers) responses in younger and older participants, respectively, with seroconversion rates of 100% in both age groups. Neutralizing antibody responses exceeded those seen in convalescent sera for both age groups.

Conclusions

The study confirmed that the two-dose regimen of 5-µg NVX-CoV2373 is highly immunogenic and well tolerated in both younger and older participants.

(Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number: NCT04368988).
How does the magnitude of genetic variation affect eco-evolutionary dynamics in character displacement?
Authors: Morita Keiichi , Yamamichi Masato
Published: March 2021

Abstract

While previous studies on character displacement tended to focus on trait divergence and convergence as a result of long-term evolution, recent studies suggest that character displacement can be a special case of evolutionary rescue, where rapid evolution prevents population extinction by weakening negative interspecific interactions. When the magnitude of genetic variation is small, however, the speed of trait divergence can be slow and populations may go extinct before the completion of character displacement. Here we analyzed a simple model to examine how the magnitude of genetic variation affects evolutionary rescue via ecological and reproductive character displacement that weakens resource competition and reproductive interference, respectively. We found that the large additive genetic variance is more important for preventing extinction in reproductive character displacement than in ecological character displacement. This is because reproductive interference produces a locally stable coexistence equilibrium with positive frequency-dependence (i.e., minority disadvantage) whereas ecological character displacement results in a globally stable coexistence equilibrium. Furthermore, population extinction becomes less likely when ecological and reproductive character displacement occur simultaneously due to positive covariance between ecological and reproductive traits. Our results suggest that while reproductive character displacement may be rarer than ecological character displacement, it is more likely to occur when there exists positive trait covariance, such as the case of a magic trait in reinforcement of speciation processes.
Healthcare utilisation survey as part of the Hybrid model of the Surveillance of Enteric Fever in India (SEFI) study: processes, results, and challenges
Authors: Raju Reshma , Angelin J Kezia , Karthikeyan Arun S , Kumar Dilesh , Kumar Ranjith R , Sahai Nikhil , Ramanujan Karthik , Murhekar Manoj , Elangovan A. , Samuel Prasanna , John Jacob , Kang Gagandeep
Published: March 2021

Background

Enteric fever is a significant health challenge in low and middle-income countries. “Surveillance of Enteric Fever in India” (SEFI) network was set up to obtain reliable incidence data. Six sites utilised a hybrid surveillance model, a combination of facility-based surveillance and community-based healthcare utilisation survey (HCUS). HCUS was performed to determine the percentage of the catchment population utilising the study facilities for febrile episodes, and is described here.

Methods

A two-stage sampling process was utilised for the HCUS to select 5000 households per site. Demographic data and healthcare-seeking behaviour were assessed.

Results

Febrile hospitalisation rate ranged from 2.5/1000 in Kullu to 9.6/1000 in Anantapur. The percentage of febrile admissions that sought care in the study hospital from the catchment area is 17% in Anantapur, 38% in Karimganj, 38% in Chandigarh, 10% in Nandurbar, 36% in Kullu and 24% in East Champaran respectively.

Conclusions

The variability in healthcare utilisation for fever admissions in the study hospitals underscores the importance of periodic healthcare utilisation surveys in hybrid surveillance. It is essential to adjust for those cases which have slipped out of the facility surveillance radar for obtaining an accurate estimate of the disease burden.