bluuebunny/crossref_metadata_2025 huggingface dataset:
Exponential growth of hadal science: perspectives and future directions identified using topic modelling
Authors: Weston Johanna N J , Jamieson Alan J
Published: April 2022

The hadal zone is a cluster of deep-ocean habitats that plunge to depths of 6000–11000 m below sea level. Research of the deepest marine zone has occurred on a disjunct timeline and slower than shallower zones. Over the past 20 years, research efforts have surged with greater sampling capabilities and an expansion of expeditions. We aimed to assess the state of hadal science by quantitively assessing the publishing landscape. We applied a topic modelling approach and fit a Latent Dirichlet Allocation model for 12 topics to 520 abstracts from peer-reviewed papers, reviews, and conference proceedings available on the Web of Science's Core Collection between 1991 and 2021. The model outputs were analysed with ecological modelling approaches to identify the main lines of research, track trends over time, and identify strengths and gaps. We found that hadal science is occurring across all five broad disciplines of oceanography and engineering. Hadal research has exponentially grown in the past 30 years, a trend that shows no signs of slowing. The expansion is most rapidly occurring to understand the biogeochemistry of trenches, the functions of microbial communities, and the unique biodiversity inhabiting these ecosystems, and then the application of ‘omics techniques to understand hadal life. The topic trends over time are largely driven by available technology to access and sample the deepest depths and not necessarily the pursuit of specific scientific questions, i.e. the hadal research topics are bounded by the capabilities of available exploratory vehicles. We propose three recommendations for future hadal research: (1) conduct multifeature studies that include all hadal geomorphologies across their depth range, (2) establish a programme for seasonal or long-term sampling, and (3) strengthen cross-disciplinary research. This continued acceleration in hadal research is pertinent for this last marine frontier given its vulnerability to multiple anthropogenic pressures and cascading threats from global change.
An assessment of sampling approaches for estimating growth from fishery-dependent biological samples
Authors: Schemmel Eva , Bohaboy Erin C , Kinney Michael J , O'Malley Joseph M
Published: April 2022

Accuracy of fish growth estimates depends greatly on how samples are collected. A total of three common sampling strategies are random, fixed otolith sampling (FOS), and proportional otolith sampling (POS). Random sampling is inefficient and rarely random. While POS has been shown to produce more accurate estimates of growth compared to FOS under ideal conditions, it is unclear how variables such as sample size, fishery selectivity, and fishing mortality influence sampling bias. Simulated age-at-length observations from two tropical deepwater species were used to evaluate the accuracy of von Bertalanffy growth parameter estimates comparing FOS and POS for a fast-growing, short-lived fish (Prisitipomoides auricilla) and a slow-growing, long-lived fish (Etelis coruscans). A total of 24 scenarios were tested to examine the influence of sample size, minimum size selected in the fishery, fishery exploitation rates, and supplemental sampling on growth parameter estimates. Furthermore, tests were applied to real fishery age–length observations for P. auricilla. POS consistently performed better than FOS, especially when the catch was representative of the population. However, FOS performed better when catch was not representative. This research demonstrates the importance of considering effects of fishery selectivity, fishing mortality, and sample size on sampling strategy and provides a tool to select an appropriate approach.
Navigating law’s complexities: Concepts for postnational law—A reply to Nico Krisch
Authors: Taekema Sanne
Published: April 2022

In this Reply to the article by Nico Krisch, the idea of entangled legalities is questioned from a theoretical point of view. Pointing out entanglement empirically is not enough to give the concept body; it needs to be embedded in a theory of law. Elaborating Krisch’s critique on seeing law as a system, I argue that entanglement implies a concept of law that is practice-based: a shift from norms to what actors do with law. A practice-based view of law focuses on interactions between actors, highlighting the social and value-laden character of law. This reconceptualizes systemic thinking as a tradition that has developed in legal practices and broadens the concept of law to include postnational phenomena as an integral part of what law is. Using an example from climate change litigation, I argue that this conceptualization tracks normative claims by legal actors that no longer make a sharp distinction between formal legal norms and other normative standards. Combining entanglement and law as practice thus helps to make sense of postnational legal practices.
Third-Party Funding in Investment Arbitration: How to Define and Disclose It
Authors: Kayalı Didem
Published: April 2022

The provision of funds by non-parties to pursue or defend a dispute, namely third-party funding, has become a focal point in investment arbitration because of participation of States, and the high value of disputes and thus expenses. However, since there are different kinds of external financing such as insurance contracts, contingency and conditional fee arrangements and loans by financial institutions, there is no consensus with regard to the definition of the concept either in literature or in practice. Besides, due to the possibility of connection between the funders and the arbitrators, disclosure of any funding arrangement is considered necessary to refrain from potential conflicts of interest that may harm the integrity of the arbitration process. Yet again, there are different approaches to the issue. After examining various definitions used in national and international regulations, investment treaties, related reports, rules of arbitration institutions and academic literature, this article seeks to offer an operational definition of the concept. While doing that, it suggests a perspective of differentiating agreements with professionals whose motivation is to make an investment from other means of external financing. Considering the importance of independence and impartiality of arbitrators and the need for statistical data to evaluate the link between third-party funding and the number of cases in investment arbitration, the article acknowledges the necessity for disclosure of third-party funding. Going one step further, it modestly proposes a model provision regarding definition and disclosure of third-party funding to clarify the requirement of disclosure.
Surgical and interventional rescue strategies for Fontan failure
Authors: Gierlinger Gregor , Sames-Dolzer Eva , Kreuzer Michaela , Mair Roland , Nawrozi Mohammad-Paimann , Tulzer Andreas , Bauer Christoph , Tulzer Gerald , Mair Rudolf
Published: April 2022

OBJECTIVES

Fontan patients are at lifelong risk for developing complications, which may result in Fontan failure. Survival rates after heart transplantation (HTX) are still unsatisfying in these patients. Long-term survival of extracardiac Fontan patients in the modern era was investigated. The objective of this study was to investigate if surgical and interventional procedures in patients with protein-losing enteropathy (PLE) and/or plastic bronchitis (PB) and a failing Fontan circulation can postpone or avoid HTX.

METHODS

Retrospective data collection of all children who underwent a Fontan procedure between January 1999 and July 2021 at our centre was performed. Patients were surveyed regarding the occurrence of PLE or PB and their outcome was reported descriptively. HTX-free survival of patients who underwent a rescue procedure due to PLE/PB was evaluated.

RESULTS

Three hundred and seventy [94.1% (95% confidence interval, 91.4–96.3)] Fontan patients were free of HTX or death at last follow-up after a median follow-up time of 6.7 years. PB/PLE was diagnosed in 34 patients during the observation period. A rescue procedure was undertaken in 16 pts. at a median time of 6.5 months (range: 1 day to 9.4 years) since the initial diagnosis of PLE/PB. In these patients, HTX-free survival was 75% (95% confidence interval, 47.6–92.7) at a median follow-up time of 4.0 years after the procedure. Range: 3.5 months to 13.9 years.

CONCLUSIONS

Extracardiac Fontan patients in the modern era expect reasonable HTX-free survival rates. Surgical and/or interventional rescue strategies for Fontan failure can postpone HTX for a sustained period of time.
Pathway-specific population attributable fractions
Authors: O’Connell Maurice M , Ferguson John P
Published: April 2022

Introduction

A population attributable fraction represents the relative change in disease prevalence that one might expect if a particular exposure was absent from the population. Often, one might be interested in what percentage of this effect acts through particular pathways. For instance, the effect of a sedentary lifestyle on stroke risk may be mediated by blood pressure, body mass index and several other intermediate risk factors.

Methods

We define a new metric, the pathway-specific population attributable fraction (PS-PAF), for mediating pathways of interest. PS-PAFs can be informally defined as the relative change in disease prevalence from an intervention that shifts the distribution of the mediator to its expected distribution if the risk factor were eliminated, and sometimes more simply as the relative change in disease prevalence if the mediating pathway were disabled. A potential outcomes framework is used for formal definitions and associated estimands are derived via relevant identifiability conditions. Computationally efficient estimators for PS-PAFs are derived based on these identifiability conditions.

Results

Calculations are demonstrated using INTERSTROKE—an international case–control study designed to quantify disease burden attributable to a number of known causal risk factors. The applied results suggest that mediating pathways from physical activity through blood pressure, blood lipids and body size explain comparable proportions of stroke disease burden, but a large proportion of the disease burden due to physical inactivity may be explained by alternative pathways.

Conclusion

PS-PAFs measure disease burden attributable to differing mediating pathways and can generate insights into the dominant mechanisms by which a risk factor affects disease at a population level.
Blood D-Amino Acid Oxidase Levels Increased With Cognitive Decline Among People With Mild Cognitive Impairment: A Two-Year Prospective Study
Authors: Lin Chieh-Hsin , Lane Hsien-Yuan
Published: April 2022

Background

Dysregulation of N-methyl-D-aspartate receptor (NMDAR) neurotransmission has been reported to be implicated in the pathogenesis of Alzheimer’s disease (AD). D-amino acid oxidase (DAO), responsible for degradation of NMDAR-related D-amino acids such as D-serine, regulates NMDAR function. A cross-section study found that serum DAO levels were positively related with the severity of cognitive aging among elderly individuals. This 2-year prospective study aimed to explore the role of DAO levels in predicting the outcome of patients with very early-phase AD, such as mild cognitive impairment (MCI).

Methods

Fifty-one patients with MCI and 21 healthy individuals were recruited. Serum DAO levels and cognitive function, measured by the AD assessment scale-cognitive subscale and the Mini-Mental Status Examination, were monitored every 6 months. We employed multiple regressions to examine the role of DAO concentration in cognitive decline in the 2-year period.

Results

From baseline to endpoint (24 months), serum DAO levels increased significantly, and cognitive ability declined according to both cognitive tests in the MCI patients. Among the healthy individuals, DAO concentrations also increased and Mini-Mental Status Examination scores declined; however, AD assessment scale-cognitive subscale scores did not significantly change. Further, DAO levels at both months 12 and 18 were predictive of cognitive impairment at month 24 among the MCI patients.

Conclusions

To our knowledge, this is the first study to demonstrate that blood DAO levels increased with cognitive deterioration among the MCI patients in a prospective manner. If replicated by future studies, blood DAO concentration may be regarded as a biomarker for monitoring cognitive change in the patients with MCI.
Interventions to improve medicines optimisation in older people with frailty in primary care: a systematic review
Authors: Faulkner Lucy , Hughes Carmel M , Barry Heather E
Published: April 2022

Objectives

To identify studies that delivered an intervention to frail older people to improve medicines optimisation; identify the outcomes reported in these studies; and assess the effectiveness of these interventions on chosen study outcomes.

Method

Eight electronic databases and four trial registries were systematically searched from the date of inception to April 2020. Inclusion criteria were randomised controlled trials and non-randomised studies of interventions to improve medicines optimisation (including administration, adherence, deprescribing, prescribing and/or medication review) in community-dwelling older people (aged ≥65 years) with a frailty diagnosis. Only studies published in English were included. A narrative synthesis was conducted, and quality was assessed using an appropriate risk of bias tool.

Key findings

Searches identified 601 articles; one study met the criteria for inclusion. The single eligible study used a quasi-experimental pre-test–post-test study design to evaluate the impact of a pharmacist-led, team-based medication review for 54 frail older patients living in primary care. Improvements in the total number of medications and prescribing appropriateness were observed. The study was judged to be at an overall serious risk of bias.

Conclusion

There is a dearth of high-quality evidence demonstrating the effectiveness of medicines optimisation interventions for older people with frailty within primary care. Due to the strong association between patients’ level of frailty and adverse outcomes, it is important that future research focuses on proactive interventions which may be beneficial to this patient population.
Impact of pharmacist medication review for paediatric patients: an observational study
Authors: Solano Marine , Jeannin Marie , Anxionnat Raphael , Vardanega Julie , Ridley Ashley , Amsallem Daniel , Limat Samuel , Clairet Anne-Laure
Published: April 2022

Background

Paediatric patients are at high risk of medication errors and adverse drug events due to complex medical care.

Objective

To assess the impact of pharmacist medication review for paediatric patients.

Setting

A single-centre prospective observational study was performed over 33 months, from February 2018 to October 2020 in a French Hospital.

Method

Clinical pharmacists provided medication counselling at a hospital and conducted telephone follow-ups between 3 and 7 days after discharge of paediatric patients with chronic diseases for whom treatment was introduced or modified during hospitalisation or hospital consultations.

Main outcome measures

The incidence of drug-related problems (DRPs), the number and type of pharmacist intervention and paediatrician acceptance rates were assessed. Parents’ understanding and drug-related needs were compared before and after medication review. Time to outpatient treatment and patient satisfaction were determined. Statistical analyses were performed in Excel.

Results

In total, 195 paediatric patients were included. Pharmacists identified 65 interventions, 95% of which were accepted. The most frequent DRPs included inappropriate drug administration (32.3%), herb–drug interactions (24.6%) and dose selection (17%). Parents’ knowledge increased by 28% from baseline after pharmacist’s medication counselling. Parents’ drug-related needs concerning administration and side effects decreased by 67% and 49%, respectively, following the pharmacist’s medication counselling. Most (75%) of the patients were able to get their treatment immediately after discharge.

Conclusion

Clinical pharmacists can improve medication safety for children during the discharge process or consultations, by reducing prescription errors, optimising administration, counselling patients or parents and helping to ensure care continuity.
Moving beyond sub-Gaussianity in high-dimensional statistics: applications in covariance estimation and linear regression
Authors: Kuchibhotla Arun Kumar , Chakrabortty Abhishek
Published: April 2022

Concentration inequalities form an essential toolkit in the study of high-dimensional statistical methods. Most of the relevant statistics literature in this regard is, however, based on the assumptions of sub-Gaussian or sub-exponential random variables/vectors. In this paper, we first bring together, through a unified exposition, various probabilistic inequalities for sums of independent random variables under much more general exponential type (namely sub-Weibull) tail assumptions. These results extract a part sub-Gaussian tail behavior of the sum in finite samples, matching the asymptotics governed by the central limit theorem, and are compactly represented in terms of a new Orlicz quasi-norm—the Generalized Bernstein–Orlicz norm—that typifies such kind of tail behaviors.

We illustrate the usefulness of these inequalities through the analysis of four fundamental problems in high-dimensional statistics. In the first two problems, we study the rate of convergence of the sample covariance matrix in terms of the maximum elementwise norm and the maximum $k$-sub-matrix operator norm that are key quantities of interest in bootstrap procedures and high-dimensional structured covariance matrix estimation, as well as in high-dimensional and post-selection inference. The third example concerns the restricted eigenvalue condition, required in high-dimensional linear regression, which we verify for all sub-Weibull random vectors through a unified analysis, and also prove a more general result related to restricted strong convexity in the process. In the final example, we consider the Lasso estimator for linear regression and establish its rate of convergence to be generally $\sqrt{k\log p/n}$, for $k$-sparse signals, under much weaker than usual tail assumptions (on the errors as well as the covariates), while also allowing for misspecified models and both fixed and random design. To our knowledge, these are the first such results for Lasso obtained in this generality. The common feature in all our results over all the examples is that the convergence rates under most exponential tails match the usual (optimal) ones obtained under sub-Gaussian assumptions. Finally, we also establish some complementary results on analogous tail bounds for the suprema of empirical processes indexed by sub-Weibull variables. All our results are finite samples.
A manifold inexact augmented Lagrangian method for nonsmooth optimization on Riemannian submanifolds in Euclidean space
Authors: Deng Kangkang , Peng Zheng
Published: April 2022

We develop a manifold inexact augmented Lagrangian framework to solve a family of nonsmooth optimization problem on Riemannian submanifold embedding in Euclidean space, whose objective function is the sum of a smooth function (but possibly nonconvex) and a nonsmooth convex function in Euclidean space. By utilizing the Moreau envelope, we get a smoothing Riemannian minimization subproblem at each iteration of the proposed method. Consequentially, each iteration subproblem is solved by a Riemannian Barzilai–Borwein gradient method. Theoretically, the convergence to critical point of the proposed method is established under some mild assumptions. Numerical experiments on compressed modes problems in physic and sparse principal component analysis demonstrate that the proposed method is a competitive method compared with some state-of-the-art methods.
Mixed virtual element method for the Helmholtz transmission eigenvalue problem on polytopal meshes
Authors: Meng Jian , Wang Gang , Mei Liquan
Published: April 2022

In this paper we propose and analyze a mixed virtual element method for the Helmholtz transmission eigenvalue problem, which is a fourth order, nonlinear and non-self-adjoint eigenvalue problem and is important in the inverse scattering theory. The conforming virtual element is used for discretization. We prove correct spectral approximation and error estimates of the discrete scheme. Finally, we show several numerical examples to verify the theoretical results and present the performance of different stabilization parameters and the comparison with the $C^{1}$ virtual element method.
Geometry of Genus One Fine Compactified Universal Jacobians
Authors: Pagani Nicola , Tommasi Orsola
Published: April 2022

We introduce a general abstract notion of fine compactified Jacobian for nodal curves of arbitrary genus. We focus on genus $1$ and prove combinatorial classification results for fine compactified Jacobians in the case of a single nodal curve and in the case of the universal family $\overline {{\mathcal {C}}}_{1,n} / \overline {{\mathcal {M}}}_{1,n}$ over the moduli space of stable pointed curves. We show that if the fine compactified Jacobian of a nodal curve of genus $1$ can be extended to a smoothing of the curve, then it can be described as the moduli space of stable sheaves with respect to some polarisation. In the universal case we construct new examples of genus $1$ fine compactified universal Jacobians. Then we give a formula for the Hodge and Betti numbers of each genus $1$ fine compactified universal Jacobian $\overline {{\mathcal {J}}}^{d}_{1,n}$ and prove that their even cohomology is algebraic.
Extensions of C*-Algebras by a Small Ideal
Authors: Lin Huaxin , Ng Ping
Wong
Published: April 2022

We classify all essential extensions of the form $$ \begin{align*} &0 \rightarrow {\mathcal{W}} \rightarrow {D} \rightarrow A \rightarrow 0,\end{align*}$$where ${\mathcal {W}}$ is the unique separable simple C*-algebra with a unique tracial state, which is $KK$-contractible and has finite nuclear dimension, and $A$ is a separable amenable ${\mathcal {W}}$-embeddable C*-algebra, which satisfies the Universal Coefficient Theorem (UCT). We actually prove more general results. We also classify a class of amenable $C^*$-algebras, which have only one proper closed ideal ${\mathcal {W}}.$
Favipiravir Treatment of Uncomplicated Influenza in Adults: Results of Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials
Authors: Hayden Frederick G , Lenk Robert P , Stonis Lucille , Oldham-Creamer Catherine , Kang Lih Lisa , Epstein Carol
Published: April 2022

Background

We conducted double-blind, placebo-controlled trials assessing the efficacy and tolerability of favipiravir in acute influenza.

Methods

Otherwise healthy adults with influenza-like symptoms and fever of ≤48 hours were randomized to favipiravir (1800 mg twice daily [BID] on day 1, 800 mg BID on days 2–5) or placebo tablets (1:1 in US316; 3:1 in US317). The primary efficacy endpoint was the time to illness alleviation when 6 influenza symptoms were self-rated as absent or mild and fever was absent in the intention-to-treat, influenza-infected participants.

Results

In US316 (301 favipiravir, 322 placebo), favipiravir was associated with a 14.4-hour reduction (median, 84.2 vs 98.6 hours; P = .004) in time to illness alleviation vs placebo. In US317 (526 favipiravir, 169 placebo), favipiravir did not significantly reduce time to alleviation (median, 77.8 vs 83.9 hours). In both trials favipiravir was associated with reduced viral titers, RNA load area under the curve over days 1–5, and median times to cessation of virus detection (P < .001). Aside from asymptomatic hyperuricemia, no important differences in adverse events were found.

Conclusions

This favipiravir dosing regimen demonstrated significant antiviral efficacy but inconsistent illness alleviation in uncomplicated influenza. Studies of higher doses and antiviral combinations for treating serious influenza and other RNA viral infections are warranted.

Clinical Trials Registration. NCT02026349; NCT02008344.
A Retrospective Cohort Study on Infant Respiratory Tract Infection Hospitalizations and Recurrent Wheeze and Asthma Risk: Impact of Respiratory Syncytial Virus
Authors: van Wijhe Maarten , Johannesen Caroline Klint , Simonsen Lone , Jørgensen Inger Merete ,   the RESCEU Investigators, Nair Harish , Campbell Harry , Beutels Philippe , Bont Louis , Pollard Andrew , Openshaw Peter , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea K , van den Berge Maarten , Giaquinto Carlo , Abram Michael , Swanson Kena , Rizkalla Bishoy , Vernhes Charlotte , Gallichan Scott , Aerssens Jeroen , Kumar Veena , Molero Eva , Fischer Thea K
Published: April 2022

Background

Infant respiratory syncytial virus infection (RSV) has been associated with asthma later in life. We explored the risk of recurrent wheeze or asthma in children with infant RSV-associated hospitalization compared to other respiratory infections.

Methods

We performed a retrospective cohort study using Danish national hospital discharge registers. Infants younger than 6 months, born between January 1995 and October 2018, and with a RSV hospital admission were compared to infants hospitalized for injuries, non-RSV acute upper respiratory tract infection (AURTI), pneumonia and other respiratory pathogens, nonpathogen-coded lower respiratory tract infections (LRTI), pertussis, or nonspecific respiratory infections. Infants were followed until recurrent wheeze or asthma diagnosis, death, migration, age 10 years, or study end. We estimated cumulative incidence rate ratios (CIRR) and hazard ratios (HR) adjusted for sex, age at inclusion, hospital length of stay (LOS), maternal smoking, 5-minute APGAR score (APGAR5), prematurity, and congenital risk factors (CRF).

Results

We included 68 130 infants, of whom 20 920 (30.7%) had RSV hospitalization. The cumulative incidence rate of recurrent wheeze or asthma was 16.6 per 1000 person-years after RSV hospitalization, higher than after injury (CIRR, 2.69; 95% confidence interval [CI], 2.48–2.92), AURTI (CIRR, 1.48; 95% CI, 1.34–1.58), or pertussis (CIRR, 2.32; 95% CI, 1.85–2.91), similar to pneumonia and other respiratory pathogens (CIRR, 1.15; 95% CI, .99–1.34) and LRTI (CIRR, 0.79; 95% CI, .60–1.04), but lower than nonspecific respiratory infections (CIRR, 0.79; 95% CI, .73–.87). Adjusted HRs for recurrent wheeze or asthma after RSV hospitalization compared to injuries decreased from 2.37 (95% CI, 2.08–2.70) for 0 to <1 year to 1.23 (95% CI, .88–1.73) for 6 to <10 years for term-born children, and from 1.48 (95% CI, 1.09–2.00) to 0.60 (95% CI, .25–1.43) for preterm-born children. Sex, maternal smoking, LOS, CRF, and APGAR5 were independent risk factors.

Conclusions

Infant RSV hospitalization is associated with recurrent wheeze and asthma hospitalization, predominantly at preschool age. If causal, RSV prophylaxis, including vaccines, may significantly reduce disease burden of wheeze and asthma.
Which vaccination strategy against COVID-19?
Authors: De Matteis Alessandro , Turkmen Ceylan Fethiye B , Urpis Enrico
Published: April 2022

Background

Bottlenecks in the production and supply pipeline of vaccines against coronavirus disease 2019 have led some countries to consider the option of dose-sparing strategies (e.g., increasing the number of people who receive some vaccine by halving the dose or increasing the interval between doses). In this study we assess the contribution of vaccination strategies to reducing the mortality induced by severe acute respiratory syndrome coronavirus 2.

Methods

This study focuses on the evolution of the pandemic and related vaccination efforts in five countries that have adopted different vaccination strategies or have experienced a bottleneck in their vaccine supply. The analysis is conducted using an autoregressive time-series approach through a system of simultaneous equations.

Results

The outcome of the early months of the vaccination campaign in containing the number of deaths induced by the epidemic varies across our sample. Overall, our results highlight the effective role played by the vaccine in containing the death toll induced by the epidemic. We could not find evidence of reduced effectiveness of the second dose in the presence of an extended inter-dose interval. The effectiveness of the vaccination campaign results appears to be strongly affected by the stability of vaccine supply.

Conclusions

The vaccine is effective in containing the deaths caused by the virus, particularly when multiple doses have been administered. The stability of the vaccine pipeline plays a critical role in determining the effectiveness of the vaccination campaign.
Regional and socio-economic disparity in use of insecticide-treated nets to prevent malaria among pregnant women in Kenya
Authors: Haileselassie Werissaw , Habtemichael Mizan , Adam Ruth , Haidar Jemal , David Randy E , Belachew Ayele , Mengesha Abenet Tafesse , Koepfli Cristian , Deressa Wakgari , Parker Daniel M , Kassaw Nigussie Assefa
Published: April 2022

Background

Insecticide-treated net (ITN) use is among the most recommended strategies to prevent malaria in pregnancy. We analysed the regional and socio-economic patterns of ITN use among pregnant women in Kenya using data from the 2003, 2008 and 2014 Kenyan Demographic and Health Surveys (KDHSs).

Methods

Inequality was assessed using four dimensions: economic status, education, place of residence and region. Both relative and absolute summary measures were applied. In addition, simple and complex summary measures, i.e. difference, population attributable fraction, population attributable risk and ratio were considered based on the number of subgroups in each variable.

Results

There was overt inequality in the use of ITNs among pregnant women, with greater use among the better-off group in 2003 and 2014. Greater ITN use was also observed among pregnant women with a higher level of education. Pregnant women from urban settings tended to use ITNs (slept under a net the night before the survey) more than their rural counterparts in the 2003 KDHS. There were significant regional variations across the three surveys in all inequality summary measures, except ratio in the 2014 survey.

Conclusions

Significant inequality in ITN use among pregnant women was observed at a macro scale.
Anti-tumor immunity by transcriptional synergy between TLR9 and STING activation
Authors: Temizoz Burcu , Hioki Kou , Kobari Shingo , Jounai Nao , Kusakabe Takato , Lee Michelle S J , Coban Cevayir , Kuroda Etsushi , Ishii Ken J
Published: April 2022

Agonists for TLR9 and stimulator of IFN genes (STING) offer therapeutic applications as both anti-tumor agents and vaccine adjuvants, though their clinical applications are limited; the clinically available TLR9 agonist is a weak IFN inducer and STING agonists induce undesired type 2 immunity. Yet, combining TLR9 and STING agonists overcame these limitations by synergistically inducing innate and adaptive IFNγ to become an advantageous type 1 adjuvant, suppressing type 2 immunity, in addition to exerting robust anti-tumor activities when used as a monotherapeutic agent for cancer immunotherapy. Here, we sought to decipher the immunological mechanisms behind the synergism mediated by TLR9 and STING agonists and found that their potent anti-tumor immunity in a Pan02 peritoneal dissemination model of pancreatic cancer was achieved only when agonists for TLR9 and STING were administered locally, and was via mechanisms involving CD4 and CD8 T cells as well as the co-operative action of IL-12 and type I IFNs. Rechallenge studies of long-term cancer survivors suggested that the elicitation of Pan02-specific memory responses provides protection against the secondary tumor challenge. Mechanistically, we found that TLR9 and STING agonists synergistically induce IL-12 and type I IFN production in murine APCs. The synergistic effect of the TLR9 and STING agonists on IL-12p40 was at protein, mRNA and promoter activation levels, and transcriptional regulation was mediated by a 200 bp region situated 983 bp upstream of the IL-12p40 transcription initiation site. Such intracellular transcriptional synergy may hold a key in successful cancer immunotherapy and provide further insights into dual agonism of innate immune sensors during host homeostasis and diseases.
Wobbly Religion: Tactical Formations of Religious Idioms and Space in the Industrial Capitalist City
Authors: Callahan Richard J
Published: April 2022

This article presents an approach to studying religion, class, and labor that does not focus on workers’ religiosity or religious affiliation. Rather, through three examples from the archive of the Industrial Workers of the World in the early twentieth century, I examine religion where it flared up, not necessarily as an enduring ideology or position, but emergent in particular material settings in the context of labor protest in urban streets. The concept of wobbly religion recognizes that religion is always situated in dynamics of power, its elements available to be assembled in the name of the status quo or repurposed for tactical goals. The study of religion, this article argues, should be more attentive to the ways that the spaces of the industrial city (and any spaces, for that matter) shape the possibilities and limitations of ideological, cultural, and social expression, and the ways that tactical use of religious space and religious idioms take up and mobilize the energies of religion.
Audience, Authorship, and Agency: Religious Educational Materials for Modern Buddhist Women’s Groups in Japan
Authors: Starling Jessica
Published: April 2022

The canonical Buddhist sutras were always delivered on the occasion of a particular gathered audience. I apply this basic premise of Buddhist doctrinal production to a body of religious literature produced for women in Japan from the 1890s to the 1910s to help resolve the scholarly conundrum of how to trace female religious agency in the absence of named female authorship. I identify women’s agency as being exercised through reading rather than writing, and through gathering to listen to teachings rather than delivering sermons themselves. I conclude that providing an engaged presence for the teachings is an important form of religious agency in Buddhist and other contexts. Taking a demand-side (rather than supply-side) approach to understanding Buddhist propagation during this period also illuminates the shifting field of competition for the support and collaboration of religious women in modern Japan.
Clinical prediction scores and the utility of time to blood culture positivity in stratifying the risk of infective endocarditis in Staphylococcus aureus bacteraemia
Authors: Simos Peter A , Holland David J , Stewart Adam , Isler Burcu , Hughes Ian , Price Nathan , Henderson Andrew , Alcorn Kylie
Published: April 2022

Background

Infective endocarditis (IE) complicates up to a quarter of Staphylococcus aureus bacteraemia (SAB) cases. Risk scores predict IE complicating SAB but have undergone limited external validation, especially in community-acquired infections and those who use IV drugs. Addition of the time to positive culture (TTP) may provide incremental risk prognostication.

Objectives

To externally validate risk scores for predicting IE in SAB and assess the incremental value of TTP.

Methods

The modified Duke score was calculated for adults hospitalized with SAB at a major tertiary institution. All patients underwent echocardiography. Sensitivity and specificity of the risk scores for predicting IE were calculated, and the incremental value of TTP was assessed.

Results

One hundred and six cases were analysed and 18 (17%) met definite IE criteria. The optimal TTP to predict IE was 11.5 h (sensitivity 88.9%; specificity 71.6%). The sensitivity of VIRSTA and PREDICT (Predicting risk of endocarditis using a clinical tool) were similar (94.4% for both) and higher than POSITIVE (Prediction Of Staphylococcus aureus Infective endocarditis Time to positivity, IV drug use, Vascular phenomena, pre-Existing heart condition; 77.8%). The receiver-operator characteristic AUCs were VIRSTA 0.83, PREDICT 0.75, POSITIVE 0.89 and TTP 0.85. Adding TTP to VIRSTA (i.e. VIRSTA+) resulted in the highest AUC (0.90), sensitivity (100%) and negative predictive value (100%), albeit with a low specificity (33%).

Conclusions

The VIRSTA and POSITIVE scores were the strongest predictors for IE complicating SAB. The addition of TTP to VIRSTA (VIRSTA+) significantly improved discriminatory value and may be safely used to rationalize echocardiography strategies.
Screening for β-lactam resistance by penicillin G in the Streptococcus anginosus group challenged by rare strains with altered PBPs
Authors: Chagneau Camille V , Alcouffe Orancie , Grare Marion , Oswald Eric , Massip Clémence
Published: April 2022

Background

Streptococcus anginosus group (SAG) strains are common pathogens causing abscesses and bacteraemia. They are generally susceptible to β-lactams, which constitute first-line treatment. EUCAST recommends testing penicillin G susceptibility to screen for β-lactam resistance. Isolates categorized as susceptible (negative screening) can be reported as susceptible to aminopenicillins and third-generation cephalosporins.

Objectives

To assess the reliability of penicillin G resistance screening in predicting β-lactam resistance in SAG blood culture isolates, and to investigate isolates for which this test would be unreliable.

Methods

We determined the susceptibility to penicillin G, amoxicillin and ceftriaxone of 90 SAG blood culture isolates, all with negative penicillin G resistance screening. β-Lactam-resistant strains were sequenced and compared with susceptible reference SAG strains.

Results

We detected two isolates displaying β-lactam resistance, especially to third-generation cephalosporins, despite negative screening for penicillin G resistance. For these isolates, amino acid substitutions were identified next to the essential PBP motifs SxxK, SxN and/or KS/TGS/T. Changes in these motifs have been previously linked to β-lactam resistance in Streptococcus pneumoniae.

Conclusions

Our study suggests that aminopenicillin and third-generation cephalosporin susceptibility should be determined for SAG strains in the event of severe infection as screening for penicillin G resistance might not be sufficient to detect resistance mechanisms that predominantly affect cephalosporins. The PBP sequencing of resistant SAG strains allowed us to detect amino acid changes potentially linked to β-lactam resistance.
Assessment of sustained efficacy and resistance emergence under human-simulated exposure of cefiderocol against Acinetobacter baumannii using in vitro chemostat and in vivo murine infection models
Authors: Gill Christian M. , Abdelraouf Kamilia , Oota Merime , Nakamura Rio , Kuroiwa Miho , Ishioka Yoshino , Takemura Miki , Yamano Yoshinori , Nicolau David P.
Published: April 2022

Objectives

This study evaluated the sustained kill and potential for resistance development of Acinetobacter baumannii exposed to human-simulated exposure of cefiderocol over 72 h in in vitro and in vivo infection models.

Methods

Seven A. baumannii isolates with cefiderocol MICs of 0.12–2 mg/L were tested. The sustained bactericidal activity compared with the initial inoculum and the resistance appearance over 72 h treatment were evaluated in both an in vitro chemostat and an in vivo murine thigh infection model under the human-simulated exposure of cefiderocol (2 g every 8 h as 3 h infusion).

Results

In the in vitro model, regrowth was observed against all seven tested isolates and resistance emergence (>2 dilution MIC increase) was observed in five test isolates. Conversely, sustained killing over 72 h and no resistance emergence were observed in six of seven tested isolates in vivo. The mechanism of one resistant isolate that appeared only in the in vitro chemostat studies was a mutation in the tonB-exbB-exbD region, which contributes to the energy transduction on the iron transporters. The resistance acquisition mechanisms of other isolates have not been identified.

Conclusions

The discrepancy in the sustained efficacy and resistance emergence between in vitro and in vivo models was observed for A. baumannii. Although the resistance mechanisms in vitro have not been fully identified, sustained efficacy without resistance emergence was observed in vivo for six of seven isolates. These studies reveal the in vivo bactericidal activity and the low potential for development of resistance among A. baumannii evaluated under human-simulated exposures.
Inclusion of social determinants of health improves sepsis readmission prediction models
Authors: Amrollahi Fatemeh , Shashikumar Supreeth P , Meier Angela , Ohno-Machado Lucila , Nemati Shamim , Wardi Gabriel
Published: April 2022

Objective

Sepsis has a high rate of 30-day unplanned readmissions. Predictive modeling has been suggested as a tool to identify high-risk patients. However, existing sepsis readmission models have low predictive value and most predictive factors in such models are not actionable.

Materials and Methods

Data from patients enrolled in the AllofUs Research Program cohort from 35 hospitals were used to develop a multicenter validated sepsis-related unplanned readmission model that incorporates clinical and social determinants of health (SDH) to predict 30-day unplanned readmissions. Sepsis cases were identified using concepts represented in the Observational Medical Outcomes Partnership. The dataset included over 60 clinical/laboratory features and over 100 SDH features.

Results

Incorporation of SDH factors into our model of clinical and demographic features improves model area under the receiver operating characteristic curve (AUC) significantly (from 0.75 to 0.80; P < .001). Model-agnostic interpretability techniques revealed demographics, economic stability, and delay in getting medical care as important SDH predictive features of unplanned hospital readmissions.

Discussion

This work represents one of the largest studies of sepsis readmissions using objective clinical data to date (8935 septic index encounters). SDH are important to determine which sepsis patients are more likely to have an unplanned 30-day readmission. The AllofUS dataset provides granular data from a diverse set of individuals, making this model potentially more generalizable than prior models.

Conclusion

Use of SDH improves predictive performance of a model to identify which sepsis patients are at high risk of an unplanned 30-day readmission.
Unlearning Ableism: Design Knowledge, Contested Models, and the Experience of Disability in 1970s Berkeley
Authors: Galán Ignacio G
Published: April 2022

This article explores the design pedagogies developed through the alliance between disability activists at the Center for Independent Living (CIL) and a number of faculty led by Raymond Lifchez at U.C. Berkeley in the 1970s and 80s. Founded by Bay Area activists including disabled students at U.C. Berkeley, the CIL provided a critical platform for advocacy and services within the disability community. In a number of seminars and studios, Lifchez and others followed the initiatives of the CIL, documented the transformation of the built environment by disabled individuals in Berkeley, and incorporated their experiences in the design process. Rather than approaching disabled individuals as bearers of special needs, a number of specific pedagogical strategies explored their expertise and resourcefulness and incorporated them as informants, consultants, and designers. Supported by archival sources, oral histories, and publications of the period, this article contributes to ongoing discussions concerning the relationship between design and the environmental and social construction of disabilities as well as to the definition of design and architecture expertise. These pedagogies critically mobilized models to advance partial and flexible design interventions and simultaneously transformed the classroom into a model that challenged the naturalization of able-bodiedness in the built environment.
Comparative Toxicity and Joint Effects of Chlorantraniliprole and Carbaryl Against the Invasive Spodioptera frugiperda (Lepidoptera: Noctuidae)
Authors: Wang Qinqin , Rui Changhui , Wang Li , Huang Weiling , Zhu Junshu , Ji Xuejiao , Yang Qingjie , Liang Pei , Yuan Huizhu , Cui Li
Published: April 2022

Fall armyworm, Spodoptera frugiperda, is one of the most devastating invasive pests in China. Chlorantraniliprole (CH) is currently the main agent for controlling S. frugiperda. Carbaryl (CA) has been widely used as a foliar treatment to control S. frugiperda, although the pest has become highly resistant to it. This study investigates the comparative toxicity and joint effects of CH and CA on S. frugiperda. Time-toxicity results showed that CH had high toxicity to 1st and 3rd instar larvae, whereas CA had very low toxicity to 1st and 3rd instar larvae. The mixtures of CH and CA at different mass ratios showed strong synergistic effects on toxicity, and the mass ratio of 2:1 exhibited the highest toxicity to S. frugiperda. Furthermore, the synergistic toxicity of CH and CA at the 2:1 mass ratio (CH+CA) was also verified in field populations of S. frugiperda. The life-history parameters showed that CH+CA dramatically decreased the survival rate and fecundity of the parent population (F0) compared with CH treatment at the same concentration. Besides, CH and CH+CA mixture showed induction effect on cytochrome P450s and glutathione-S-transferases (GSTs) activities in S. frugiperda, with cytochrome P450s enzyme responding the fastest. In conclusion, this research found CH+CA provided synergistic effects on the toxicity and the sublethal effect on larvae. The joint effects on the life-history parameters and the detoxifying enzymes in S. frugiperda, may be useful for implementing IPM programs against this Lepidoptera pest.
A Dynamic Threshold Approach for Tarnished Plant Bug (Hemiptera: Miridae) Management in the Midsouthern U.S. Cotton
Authors: Mann Ryan , Crow Whitney D , Catchot Angus L , Gore Jeff , Cook Don R , Towles Tyler
Published: April 2022

One of the most economically important pests of cotton, Gossypium hirsutum L., in the midsouth region of the United States is the tarnished plant bug, Lygus lineolaris (Palisot de Beauvois, Hemiptera: Miridae). Tarnished plant bug populations across the region have exhibited widespread resistance to numerous insecticide classes. To minimize late season resistance development, reducing unwarranted applications during the late flowering period can aid in resistance management and potentially reduce input costs. Trials were conducted during 2019 and 2020 to evaluate the impacts of tarnished plant bug populations in the later flowering period of cotton by modifying or terminating threshold regimes during the later weeks of bloom. Results showed that dynamic thresholds altered at the fourth week of bloom or later can reduce the number of late season applications made with no penalty to yield. Additionally, when utilizing a week of bloom termination approach, no significant yield losses were seen when terminating applications after the fourth week of bloom. These data may offer an alternative method to managing tarnished plant bug populations during the later flowering period of midsouth cotton.