bluuebunny/crossref_metadata_2025 huggingface dataset:
Decomposition, identification and multiply robust estimation of natural mediation effects with multiple mediators
Authors: Xia Fan , Chan Kwun Chuen Gary
Published: January 2022

Natural mediation effects are desirable estimands for studying causal mechanisms in a population, but complications arise in defining and estimating natural indirect effects through multiple mediators with an unspecified causal ordering. We propose a decomposition of the natural indirect effect of multiple mediators into individual components, termed exit indirect effects, and a remainder interaction term, and study the similarities to and differences from existing natural and interventional effects in the literature. We provide a set of identification assumptions for estimating all components of the proposed natural effect decomposition and derive the semiparametric efficiency bounds for the effects. The efficient influence functions contain conditional densities that are variationally dependent, which is uncommon in existing problems and may lead to model incompatibility. By ensuring model compatibility through a reparameterization based on copulas, our estimator is quadruply robust, which means that it remains consistent and asymptotically normal under four types of possible misspecification, and also is locally semiparametric efficient. We further propose a stabilized quadruply robust estimator to improve practical performance under possibly misspecified models, as well as a nonparametric extension based on sample splitting.
Towards Democratising Social Knowledge: A Political–Economic Analysis of the Departments of Social Work in Swiss Universities of Applied Sciences
Authors: Repetti Marion
Published: January 2022

In Switzerland, the relatively new social work departments are located in so-called universities of applied sciences (UASs), which provide a university-based and practice-oriented education. At the beginning, UASs were required to carry out ‘applied’ research and their teaching had to be ‘non-academic’, unlike in traditional universities. Although this definition is no longer present in the legal framework of tertiary education, it shapes policymakers’ representations. In reality, research and teaching agendas in UAS departments of social work have become similar to those of the social sciences departments in traditional universities. However, two aspects differentiate them from their counterparts in traditional universities and from other UAS departments today: Less research funding is available and social work students are more likely to accumulate socio-economic disadvantages compared to elsewhere. In this article, I discuss the role of social work departments in Switzerland, with a focus on the social knowledge they produce and transfer into teaching programmes and society. In addition, I use Arendt’s thoughts about knowledge, education and democracy to reflect on the existing gap between political representations of—and what takes place in—UAS departments of social work in Switzerland. The article ends with recommendations for policymakers in Switzerland and abroad.
Epilepsy imaging meets machine learning: a new era of individualized patient care
Authors: Caciagli Lorenzo , Bassett Dani S.
Published: January 2022

This scientific commentary refers to ‘Decomposing MRI phenotypic heterogeneity in epilepsy: a step towards personalized classification’ by Lee et al. (https://doi.org/10.1093/brain/awab425).
High-fat diet-induced hyperinsulinemia promotes the development of prostate adenocarcinoma in prostate-specific Pten−/− mice
Authors: Wang Hong , Yan William , Sun Yuhai , Yang Chung S
Published: January 2022

Metabolic syndrome (MetS) and its four clinical entities, central obesity, insulin resistance, hypertension and dyslipidemia, are implicated in increasing the risk and mortality of cancer in several organs. However, it is unclear how they are associated with increased risk of prostate cancer. To elucidate the mechanistic link between MetS and prostate carcinogenesis, we characterized the development of MetS and prostate adenocarcinoma in prostate-specific Pten−/− (Ptenp−/−) mice fed a high-fat (HF) diet. We found that male Ptenp−/− mice on an HF diet gained excess body weight and elevated blood glucose, insulin and insulin-like growth factor 1 (IGF1) levels at 20 weeks of age and were obese at 40 weeks. Prostate adenocarcinoma multiplicity at 40 weeks was significantly higher in the mice on an HF diet, suggesting that the HF diet promotes the development of prostate adenocarcinoma. Increased cell proliferation and enhanced AKT activation were found in the prostates of mice on an HF diet. Further transcriptome study revealed that receptor tyrosine kinase regulation, which mediates insulin/IGF1 signaling, was one of the top enriched pathways by HF diet-induced transcriptome changes. Together, our results suggest that HF diet-induced hyperinsulinemia leads to increased activation of insulin/IGF1/AKT signaling in lesioned prostates, promoting the development of adenocarcinoma.
Interleukin 17 receptor E identifies heterogeneous T helper 17 cells in peritoneal fluid of moderate and severe endometriosis patients
Authors: Jiang Yanping , Wang Lu , Peng Yaqin , Qin Jian , Tan Aili , Wang Shujun
Published: January 2022

Endometriosis is a chronic inflammatory disorder resulting in pelvic pain and infertility. The role of T helper 17 (Th17) cells in endometriosis remains elusive. In this study, through detecting CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27, RORγt-and-IL-17A-expressing Th17 cells were distinguished and sorted from peritoneal fluid (PF) of patients with stage III and IV endometriosis. Furthermore, we found that IL-17RE and CD27 were the labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27− subset, IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and IL-17RE- Th17 subset revealed up-regulation of genes involved in oxidative phosphorylation and electron transport chain in IL-17RE+ Th17 subset relative to IL-17RE− Th17 subset. Consistently, the IL-17RE+ Th17 subset produced more adenosine triphosphate (ATP) and reactive oxygen species (ROS) than IL-17RE− Th17 subset. In conclusion, this study provides a novel method to detect and isolate live PF Th17 cells from endometriosis patients and unveils the functional and metabolic heterogeneity of PF Th17 subsets. Therefore, it sheds light on the elucidation of molecular mechanisms that modulate the function of pathological Th17 cells in endometriosis.
Trends in Treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020 – July 2021
Authors: Abrams Joseph Y , Belay Ermias D , Godfred-Cato Shana , Campbell Angela P , Zambrano Laura D , Kunkel Amber , Miller Allison D , Wu Michael J , Meng Lu , Shah Ami B , Oster Matthew E
Published: January 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C.

Methods

Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention’s (CDC’s) MIS-C national surveillance system. Patients’ case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed.

Results

There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (P = .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all P < .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation.

Conclusions

IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings.
Impact of Education and Data Feedback on Antibiotic Prescribing for Urinary Tract Infections in the Emergency Department: An Interrupted Time-Series Analysis
Authors: Nys Cara L , Fischer Kristen , Funaro Jason , Shoff Christopher J , Theophanous Rebecca G , Staton Catherine A , Mando-Vandrick Jennifer , Toler Rachel , Shroba Jenny , Turner Nicholas A , Liu Beiyu , Lee Hui Jie , Moehring Rebekah W , Wrenn Rebekah H
Published: January 2022

Background

Urinary tract infections (UTIs) are often misdiagnosed or treated with exceedingly broad-spectrum antibiotics, leading to negative downstream effects. We aimed to implement antimicrobial stewardship (AS) strategies targeting UTI prescribing in the emergency department (ED).

Methods

We conducted a quasi-experimental prospective AS intervention outlining appropriate UTI diagnosis and management across 3 EDs, within an academic and 2 community hospitals, in North Carolina, United States. The study was divided into 3 phases: a baseline period and 2 intervention phases. Phase 1 included introduction of an ED-specific urine antibiogram and UTI guideline, education, and department-specific feedback on UTI diagnosis and antibiotic prescribing. Phase 2 included re-education and provider-specific feedback. Eligible patients included adults with an antibiotic prescription for UTI diagnosed in the ED from 13 November 2018 to 1 March 2021. Admitted patients were excluded. The primary outcome was guideline-concordant antibiotic use, assessed using an interrupted time-series regression analysis with 2-week intervals.

Results

Overall, 8742 distinct patients with 10 426 patient encounters were included. Ninety-two percent of all encounters (n = 9583) were diagnosed with cystitis and 8.1% with pyelonephritis (n = 843). There was an initial 15% increase in guideline-concordant antibiotic prescribing in phase 1 compared with the preintervention period (incidence rate ratio [IRR], 1.15; 95% confidence interval [CI], 1.03–1.29). A significant increase in guideline-concordant prescriptions was seen with every 2-week interval during phase 2 (IRR, 1.03; 95% CI, 1.01–1.04).

Conclusions

This multifaceted AS intervention involving a guideline, education, and provider-specific feedback increased guideline-concordant antibiotic choices for treat-and-release patients in the ED.
Lack of Access to Coronavirus Disease 2019 Vaccines Could Be a Greater Threat than Vaccine Hesitancy in Low-Income and Conflict Nations: The Case of Yemen
Authors: Noushad Mohammed , Al-Awar Mohammed Sadeg , Al-Saqqaf Inas Shakeeb , Nassani Mohammad Zakaria , Alrubaiee Gamil Ghaleb , Rastam Samer
Published: January 2022

Background

Vaccine hesitancy and vaccine inequity are 2 major hurdles toward achieving population immunity to coronavirus disease 2019 (COVID-19). Although several studies have been published on vaccine hesitancy among numerous populations, there is inadequate information on any potential correlation between vaccine acceptance and lack of access to vaccines. Our cross-sectional study in a low-income country aimed to fill this gap.

Methods

We conducted a nation-wide cross-sectional survey among the general population in Yemen, a low-income conflict country. Participants from all provinces in Yemen were included in the study. We evaluated factors that influence agreement to accept a COVID-19 vaccine and any potential correlation between vaccine hesitancy and lack of access to vaccines.

Results

Overall, 50.1% of the 5329 respondents agreed to accept a COVID-19 vaccine. Only 39.9% of participants agreed that they had access to a COVID-19 vaccine, with females indicating lower access than males. Potential determinants of vaccine acceptance included being male, updating self on the development of vaccines against COVID-19, opinion about severity of COVID-19, anxiety about contracting COVID-19, concerns about the safety of COVID-19 vaccines, and lack of access to vaccines.

Conclusions

Our results indicate that the immediate threat in Yemen toward achieving population immunity is the severe shortage and lack of access to vaccines, rather than vaccine hesitancy.
Omicron Outbreak at a Private Gathering in the Faroe Islands, Infecting 21 of 33 Triple-Vaccinated Healthcare Workers
Authors: Helmsdal Gunnhild , Hansen Olga Kristina , Møller Lars Fodgaard , Christiansen Debes Hammershaimb , Petersen Maria Skaalum , Kristiansen Marnar Fríðheim
Published: January 2022

There are concerns that the severe acute respiratory syndrome coronavirus 2 Omicron variant evades immune responses due to an unusually high number of mutations on the spike protein. Here, we report a superspreading event of Omicron infections among 21 of 33 triple-vaccinated healthcare workers who attended a private gathering.
China’s Emerging Unilateral Sanctions: Heading towards the Rule of Law?
Authors: Yu Wenjie
Published: January 2022

Although China remains consistent in its stance and practice in unilateral sanctions episodes, its ‘decade of sanctions’ has witnessed some subtle changes—in particular, its endeavour to build a rule-of-law-based unilateral sanctions regime. Both international law and the domestic law of China provide for its unilateral sanctions. It is within the discretion of China to take unilateral sanctions as long as it is not against its obligation under the applicable international law, but its domestic law shows a certain level of insufficiency. The administrative nature of unilateral sanctions decides the core parameter of due process for a rule-of-law-based unilateral sanctions regime, which has its boundaries: the limit of law as a regulatory regime for unilateral sanctions as political instrument and the limit of domestic jurisdiction in terms of extraterritorial application. To upgrade the unilateral sanctions regime according to its own concept of rule of law in foreign relations, China needs to improve the compatibility among current laws and to provide proper remedies.
Judging the Party: Public Law Wrongs and Private Law Remedies
Authors: Fu Hualing , Zhang Xianchu
Published: January 2022

This article offers a case study of civil litigation in which the decision of a Party organ or the application of Party rules in a decision have allegedly infringed the private law rights of individuals. Party organs have always performed civil activities and engaged with a wide range of civil legal relations affecting the rights and interests of various individuals and entities, resulting in occasional legal disputes between a Party organ and the aggrieved individuals or entities. After failing to challenge a Party organ’s decision within the political system, the affected member brings a case to court to challenge the validity of the decision. In the court process, legal rules are used primarily to deal with issues involving insignificant players in employment disputes with Party organs. For matters involving the Party’s own officials and those matters regarded as internal, legal rules are largely limited, if not dispensed with entirely, confirming the prerogative state’s superior position in the hierarchy above the normative state. Freedom of contract is more relevant and recognized for claims by individuals at the lower end of the political ecosystem, while politics is reserved for the elites of society and for issues where the Party is determined to maintain direct, hands-on control.
Ethnicity-dependent performance of the Global Registry of Acute Coronary Events risk score for prediction of non-ST-segment elevation myocardial infarction in-hospital mortality: nationwide cohort study
Authors: Moledina Saadiq M , Kontopantelis Evangelos , Wijeysundera Harindra C , Banerjee Shrilla , Van Spall Harriette G C , Gale Chris P , Shah Benoy N , Mohamed Mohamed O , Weston Clive , Shoaib Ahmad , Mamas Mamas A
Published: January 2022

Aims

The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with the acute coronary syndrome with or without ST-segment elevation. Little is known about its performance at predicting in-hospital mortality for ethnic minority patients.

Methods and results

We identified 326 160 admissions with non-ST-segment elevation myocardial infarction (NSTEMI) in the Myocardial Infarction National Audit Project (MINAP), 2010–17, including White (n = 299 184) and ethnic minorities (excluding White minorities) (n = 26 976). We calculated the GRACE score for in-hospital mortality and assessed ethnic group baseline characteristics by low, intermediate and high risk. The performance of the GRACE risk score was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration (calibration plots). Ethnic minorities presented younger and had increased prevalence of cardiometabolic risk factors in all GRACE risk groups. The GRACE risk score for White [AUC 0.87, 95% confidence interval (CI) 0.86–0.87] and ethnic minority (AUC 0.87, 95% CI 0.86–0.88) patients had good discrimination. However, whilst the GRACE risk model was well calibrated in White patients (expected to observed (E : O) in-hospital death rate ratio 0.99; slope 1.00), it overestimated risk in ethnic minority patients (E : O ratio 1.29; slope: 0.94).

Conclusion

The GRACE risk score provided good discrimination overall for in-hospital mortality, but was not well calibrated and overestimated risk for ethnic minorities with NSTEMI.

Key question

Does the performance of the Global Registry of Acute Coronary Events (GRACE) (v2.0) score in predicting in-hospital mortality for non-ST-segment elevation myocardial infarction (NSTEMI) differ by ethnicity?

Key finding

The GRACE risk score provided good discrimination overall for in-hospital mortality but was not well calibrated and overestimated risk for ethnic minority patients with NSTEMI.

Take-home message

Ethnicity or race should be considered during the development of risk scoring systems. Existing systems can be recalibrated in the population they serve to better address risk.
Targeted proteomics improves cardiovascular risk prediction in secondary prevention
Authors: Nurmohamed Nick S. , Belo Pereira João P. , Hoogeveen Renate M. , Kroon Jeffrey , Kraaijenhof Jordan M. , Waissi Farahnaz , Timmerman Nathalie , Bom Michiel J. , Hoefer Imo E. , Knaapen Paul , Catapano Alberico L. , Koenig Wolfgang , de Kleijn Dominique , Visseren Frank L.J. , Levin Evgeni , Stroes Erik S.G.
Published: January 2022

Aims

Current risk scores do not accurately identify patients at highest risk of recurrent atherosclerotic cardiovascular disease (ASCVD) in need of more intensive therapeutic interventions. Advances in high-throughput plasma proteomics, analysed with machine learning techniques, may offer new opportunities to further improve risk stratification in these patients.

Methods and results

Targeted plasma proteomics was performed in two secondary prevention cohorts: the Second Manifestations of ARTerial disease (SMART) cohort (n = 870) and the Athero-Express cohort (n = 700). The primary outcome was recurrent ASCVD (acute myocardial infarction, ischaemic stroke, and cardiovascular death). Machine learning techniques with extreme gradient boosting were used to construct a protein model in the derivation cohort (SMART), which was validated in the Athero-Express cohort and compared with a clinical risk model. Pathway analysis was performed to identify specific pathways in high and low C-reactive protein (CRP) patient subsets. The protein model outperformed the clinical model in both the derivation cohort [area under the curve (AUC): 0.810 vs. 0.750; P < 0.001] and validation cohort (AUC: 0.801 vs. 0.765; P < 0.001), provided significant net reclassification improvement (0.173 in validation cohort) and was well calibrated. In contrast to a clear interleukin-6 signal in high CRP patients, neutrophil-signalling-related proteins were associated with recurrent ASCVD in low CRP patients.

Conclusion

A proteome-based risk model is superior to a clinical risk model in predicting recurrent ASCVD events. Neutrophil-related pathways were found in low CRP patients, implying the presence of a residual inflammatory risk beyond traditional NLRP3 pathways. The observed net reclassification improvement illustrates the potential of proteomics when incorporated in a tailored therapeutic approach in secondary prevention patients.
Solving the eikonal equation for compressional and shear waves in anisotropic media using peridynamic differential operator
Authors: Bekar Ali Can , Madenci Erdogan , Haghighat Ehsan , Waheed Umair bin , Alkhalifah Tariq
Published: January 2022

Traveltimes of compressional (P) and shear (S) waves have proven essential in many earthquake and exploration seismology applications. An accurate and efficient traveltime computation for P and S waves is crucial for the success of these applications. However, solving the eikonal equation with a complex phase velocity field in anisotropic media is challenging. The eikonal equation is a first-order nonlinear hyperbolic partial differential equation. It represents the high-frequency asymptotic approximation of the wave equation. The fast marching and sweeping methods are commonly used due to their efficiency in numerically solving the eikonal equation. However, these methods suffer from numerical inaccuracy in anisotropic media with sharp heterogeneity, irregular surface topography and complex phase velocity fields. This study presents a new method for the solution of the eikonal equation by employing the peridynamic differential operator (PDDO). The PDDO provides the non-local form of the eikonal equation by introducing an internal length parameter (horizon) and a weight function with directional non-locality. The operator is immune to discontinuities in the form of sharp changes in field or model variables and invokes the direction of traveltime in a consistent manner. The weight function controls the strength of association among points within the horizon. Solutions are constructed in a consistent manner without upwind assumptions through simple discretization. The robustness of this approach is established by considering different types of eikonal equations on complex velocity models in anisotropic media. The examples demonstrate its unconditional numerical stability and results compare well with the reference solutions.
Who is paid in pay-for-performance? Inequalities in the distribution of financial bonuses amongst health centres in Zimbabwe
Authors: Kovacs Roxanne , Brown Garrett W , Kadungure Artwell , Kristensen Søren R , Gwati Gwati , Anselmi Laura , Midzi Nicholas , Borghi Josephine
Published: January 2022

Although pay-for-performance (P4P) schemes have been implemented across low- and middle-income countries (LMICs), little is known about their distributional consequences. A key concern is that financial bonuses are primarily captured by providers who are already better able to perform (for example, those in wealthier areas), P4P could exacerbate existing inequalities within the health system. We examine inequalities in the distribution of pay-outs in Zimbabwe’s national P4P scheme (2014–2016) using quantitative data on bonus payments and facility characteristics and findings from a thematic policy review and 28 semi-structured interviews with stakeholders at all system levels. We found that in Zimbabwe, facilities with better baseline access to guidelines, more staff, higher consultation volumes and wealthier and less remote target populations earned significantly higher P4P bonuses throughout the programme. For instance, facilities that were 1 SD above the mean in terms of access to guidelines, earned 90 USD more per quarter than those that were 1 SD below the mean. Differences in bonus pay-outs for facilities that were 1 SD above and below the mean in terms of the number of staff and consultation volumes are even more pronounced at 348 USD and 445 USD per quarter. Similarly, facilities with villages in the poorest wealth quintile in their vicinity earned less than all others—and 752 USD less per quarter than those serving villages in the richest quintile. Qualitative data confirm these findings. Respondents identified facility baseline structural quality, leadership, catchment population size and remoteness as affecting performance in the scheme. Unequal distribution of P4P pay-outs was identified as having negative consequences on staff retention, absenteeism and motivation. Based on our findings and previous work, we provide some guidance to policymakers on how to design more equitable P4P schemes.
Narrowing the gap between marine spatial planning aspirations and realities
Authors: Zuercher Rachel , Motzer Nicole , Magris Rafael A , Flannery Wesley
Published: January 2022

Many coastal nations have embraced marine spatial planning (MSP) as a solution to maintaining ecological integrity of marine environments, while ensuring continued provisioning of economic, social, and cultural benefits. However, evidence supporting the idea that plans achieve—or are likely to achieve—these goals is limited. One gap in our understanding stems from questions surrounding the metrics against which MSP success is measured. Evaluation can be based on explicitly stated objectives, or might include metrics corresponding to broad social–ecological goals. This paper compares aspirational MSP goals gleaned from a literature review to the objectives extracted from 50+ finalized and implemented plans to better understand: (1) how well these two groupings align, and (2) in what ways any misalignment may shape MSP evaluation. Findings show that plans prioritize the environment, economy, and governance, while often excluding objectives related to cultural heritage, human well-being, Indigenous rights, human safety, and climate change. Social and cultural objectives have become more prevalent over time, yet overall stated objectives remain distinct from theorized MSP goals. As international efforts aim to expand MSP, narrowing the gap between how it is perceived and how its outcomes are evaluated is critical to better understanding what it is likely to achieve.
Copepod habitat suitability estimates vary among oxygen metrics in Chesapeake Bay
Authors: Pierson James J , Testa Jeremy M , Roman Michael R
Published: January 2022

Seasonal deoxygenation in coastal and estuarine systems leads to decreased available habitat for many planktonic organisms. However, the volume of available habitat can be defined in different ways, depending on the oxygen metrics employed. Here, we used monitoring data for water quality to estimate the seasonal and inter-annual variability in habitat for the copepod Acartia tonsa in Chesapeake Bay, defined using three different oxygen metrics: a concentration-based (2 mg l−1) definition of hypoxia, and two partial pressure-based definitions corresponding to limiting oxygen demand (Pcrit), and the minimum requirement for respiration (Pleth). We examined spatial and temporal trends in the oxygen habitat, and compared habitat estimates to zooplankton abundance and distribution and in relation to hydrologically wet, average, and dry years. Pcrit predicted the largest volume of unsuitable deoxygenated habitat over space and time, and dry conditions were associated with a decreased extent of deoxygenated habitat compared to average and wet conditions. No clear relationship between copepod abundance and habitat availability was observed, but the position of peak abundance of A. tonsa correlated to the extent of deoxygenated habitat using Pcrit. Species-specific metrics to describe oxygen habitat may be more useful in understanding the non-lethal impacts of deoxygenation.
Health-related quality of life after Nuss procedure for pectus excavatum: a cross-sectional study
Authors: Norlander Louise , Sundqvist Ann-Sofie , Anderzén-Carlsson Agneta , Dreifaldt Mats , Andreasson Jesper , Vidlund Mårten
Published: January 2022

OBJECTIVES

Pectus excavatum (PE) can cause both physical and psychosocial symptoms and affect patients’ health-related quality of life. Previous international studies have shown that the Nuss procedure increases both self-esteem and body image. The aim of the study was to evaluate the health-related quality of life in patients who have undergone the Nuss procedure for PE.

METHODS

The study had a cross-sectional multicentre design. All patients (N = 420) who underwent the Nuss procedure for PE in 3 cardiothoracic departments in Sweden from 2000 to 2019 were invited to answer the RAND-36 and Nuss Questionnaire modified for adults. Genders were compared using the Mann–Whitney U-test. Patients were divided into groups based on age at time of surgery (<20, 20–30 or >30 years) and analysed by the Kruskal–Wallis H-test with post-hoc analyses.

RESULTS

A total of 236 patients returned the questionnaires; 82.2% were males. Men scored significantly better on the modified Nuss Questionnaire total (P = 0.01) and psychosocial (P = 0.02) subscales. Patients who had surgery at <20 years of age had significantly better scores on the same scales (P = 0.007 and 0.006, respectively) compared to patients aged 20–30 years at the time of surgery. However, no significant difference was seen in comparison with patients >30 years. Patients who had their bar removed had significantly better values on both scales.

CONCLUSIONS

Male gender, young age at surgery and bar removal seem to be associated with better health-related quality of life after the Nuss procedure for PE.
SARS-CoV-2 infection fatality rate after the first epidemic wave in Mexico
Authors: Torres-Ibarra Leticia , Basto-Abreu Ana , Carnalla Martha , Torres-Alvarez Rossana , Reyes-Sanchez Francisco , Hernández-Ávila Juan E , Palacio-Mejia Lina S , Alpuche-Aranda Celia , Shamah-Levy Teresa , Rivera Juan A , Barrientos-Gutierrez Tonatiuh
Published: January 2022

Background

Estimates of SARS-CoV-2 infection fatality rates (IFRs) in developing countries remain poorly characterized. Mexico has one of the highest reported COVID-19 case-fatality rates worldwide, although available estimates do not consider serologic assessment of prior exposure nor all SARS-CoV-2-related deaths. We aimed to estimate sex- and age-specific IFRs for SARS-CoV-2 in Mexico.

Methods

The total number of people in Mexico with evidence of prior SARS-CoV-2 infection was derived from National Survey of Health and Nutrition-COVID-19 (ENSANUT 2020 Covid-19)—a nationally representative serosurvey conducted from August to November 2020. COVID-19 mortality data matched to ENSANUT’s dates were retrieved from the death-certificate registry, which captures the majority of COVID-19 deaths in Mexico, and from the national surveillance system, which covers the subset of COVID-19 deaths that were identified by the health system and were confirmed through a positive polymerase chain reaction test. We analysed differences in IFRs by urbanization and region.

Results

The national SARS-CoV-2 IFR was 0.47% (95% CI 0.44, 0.50) using death certificates and 0.30% (95% CI 0.28, 0.33) using surveillance-based deaths. The IFR increased with age, being close to zero at age <30 years, but increasing to 1% at ages 50–59 years in men and 60–69 years in women, and being the highest at ≥80 years for men (5.88%) and women (6.23%). Across Mexico's nine regions, Mexico City (0.99%) had the highest and the Peninsula (0.26%) the lowest certificate-based IFRs. Metropolitan areas had higher certificate-based IFR (0.63%) than rural areas (0.17%).

Conclusion

After the first wave of the COVID-19 pandemic, the overall IFR in Mexico was comparable with those of European countries. The IFR in Mexico increased with age and was higher in men than in women. The variations in IFRs across regions and places of residence within the country suggest that structural factors related to population characteristics, pandemic containment and healthcare capabilities could have influenced lethality at the local level.
Comparative bactericidal activity of representative β-lactams against Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa
Authors: Noel Alan R , Attwood Marie , Bowker Karen E , MacGowan Alasdair P , Albur Maha
Published: January 2022

Background

There is surprisingly little comparative published data on the bactericidal action of different sub-classes of β-lactams against aerobic Gram-negative rods, and the assumption is that all behave in the same way.

Objectives

To describe a systematic investigation of a representative penicillin, cephalosporin, monobactam and carbapenem against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.

Methods

Concentration-time-kill curves (TKC) were determined for three strains each of E. coli, K. pneumoniae, A. baumannii and P. aeruginosa. All strains were susceptible to the agents used. The antibiotics were piperacillin/tazobactam, ceftazidime, aztreonam and meropenem. The initial inoculum was 106 cfu/mL and TKC were determined over 48 h. The area-under-the-bacterial-kill curve to 24 h (AUBKC 24 log cfu·h/mL) and 48 h (AUBKC 48) were used to measure antibacterial effect (ABE). Population profiles before and after antibiotic exposure were recorded.

Results

Against E. coli and K. pneumoniae meropenem had a maximal ABE at ≥MIC × 1 concentrations while piperacillin/tazobactam and ceftazidime had maximal effect at ≥MIC × 4 and aztreonam at ≥MIC × 8 concentrations. Ceftazidime, aztreonam and meropenem had less ABE against K. pneumoniae than E. coli. Against P. aeruginosa, meropenem was most bactericidal, with a maximum ABE at 8×/16 × MIC. Other β-lactams had notably less ABE. In contrast, against A. baumannii, ceftazidime and meropenem had the greatest ABE, with a maximal effect at ≥MIC × 4, concentration changes in population profiles were least apparent with E. coli.

Conclusions

β-Lactam sub-classes (penicillins, cephalosporins, monobactams and carbapenems) have different antibacterial effects against E. coli, K. pneumoniae, A. baumannii and P. aeruginosa. Extrapolation of in vitro pharmacodynamic findings from one species to another or one sub-class of β-lactam to another is not justified.
Enteral feeding tube administration with therapeutic drug monitoring of crushed posaconazole tablets and opened isavuconazonium sulfate capsules
Authors: Dieringer Thomas D , Schaenman Joanna M , Davis Matthew R.
Published: January 2022

Background

Isavuconazole and posaconazole are commonly used for both prophylaxis and treatment of invasive fungal infections. These agents are formulated for oral administration as a capsule and delayed release (DR) tablet or suspension, respectively. In patients unable to swallow, alternative means of administration, such as crushing posaconazole DR tablets and opening isavuconazole capsules, may be used to avoid IV administration or use of posaconazole suspension, which often produces subtherapeutic concentrations.

Objectives

To assess the feasibility of achieving target plasma drug concentrations with enteral feeding tube (EFT) administration of crushed posaconazole DR tablets and opened isavuconazole capsules.

Methods

We retrospectively reviewed pharmacy records to identify patients receiving EFT administration of posaconazole or isavuconazole with concurrent therapeutic drug monitoring from October 2019 to June 2021. Plasma concentrations of either agent as well as clinical outcomes were documented.

Results

We identified 37 patients receiving 38 courses of EFT isavuconazole or posaconazole. The majority of patients received primary prophylaxis following lung transplantation (64.9%). Plasma concentrations upon first assessment were therapeutic in the majority of patients (posaconazole 71.5%, isavuconazole 83.3%) with a mean level of 1.61 ± 0.77 mg/L for posaconazole and 2.07 ± 1.1 mg/L for isavuconazole. Of those that were subtherapeutic on initial assessment, all but one subsequently achieved target levels upon dose titration. Standard maintenance doses were used in all isavuconazole and most posaconazole patients.

Conclusions

Our case series demonstrates that isavuconazole and posaconazole can be administered via EFT with concurrent therapeutic drug monitoring to achieve target plasma concentrations in the majority of patients.
Genome survey sequencing of the long-legged spiny lobsterPanulirus longipes(A. Milne-Edwards, 1868) (Decapoda: Achelata: Palinuridae): improved mitochondrial genome annotation, nuclear repetitive elements classification, and SSR marker discovery
Authors: Baeza J Antonio , Baker A M , Liu Hongtao
Published: January 2022

The long-legged spiny lobster Panulirus longipes (A. Milne-Edwards, 1868) inhabits shallow water rock and coral reefs in the Indo-West Pacific region and is currently targeted by local fisheries along most of its range of distribution. This study conducted, for the first time, a genome survey in P. longipes. Using low coverage short Illumina 150 bp pair-end reads sequencing, we assembled, annotated, and manually curated the mitochondrial genome, described nuclear repetitive elements, and discovered microsatellites (SRR). The pipeline NOVOPlasty assembled the complete mitochondrial genome of P. longipes (coverage = 551×). The mitochondrial genome of P. longipes is 15,739 bp in length and comprised of 13 protein coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. A single 804 bp long intergenic space is assumed to be the control region. The secondary structures of the tRNA genes exhibit a standard “cloverleaf” structure, with the exception of trnS1 that is missing the DHU arm. A large portion of repetitive sequences (~56%) was detected in the nuclear genome of P. longipes and many repetitive elements could not be assigned to known families. Taking into account only annotated repetitive elements, the most common belong to Class I-Long Interspersed Nuclear Element (LINE) and Satellite DNA which are considerably more abundant than Class I-Penelope and Class I-LTR Ty3-gypsy elements. Three clusters were classified as 45S rDNA. A total of 18 SSRs were identified. These newly developed genomic resources will contribute to clarifying the putative existence of cryptic species or subspecies, developing conservation plans, and managing the fishery of the long-legged spiny lobster Panulirus longipes.
Early Stimulation and Nutrition: The Impacts of a Scalable Intervention
Authors: Attanasio Orazio , Baker-Henningham Helen , Bernal Raquel , Meghir Costas , Pineda Diana , Rubio-Codina Marta
Published: January 2022

Early childhood development is becoming the focus of policy worldwide. However, the evidence on the effectiveness of scalable models is scant, particularly when it comes to infants in developing countries. In this paper, we describe and evaluate with a cluster-Randomized Controlled Trial an intervention designed to improve the quality of child stimulation within the context of an existing parenting program in Colombia, known as FAMI. The intervention improved children’s development by 0.16 of a standard deviation (SD) and children’s nutritional status, as reflected in a reduction of 5.8 percentage points of children whose height-for-age is below -1 SD.
Pulse width research on half-sine excitation signal for bending vibrator
Authors: Zhang Kai , Li Fengbo , Wu Jinping , Tan Baohai , Liu Lei
Published: January 2022

Acoustic well logging adopts bending vibrators to transform high-voltage electric signals into acoustic signals. Excited acoustic signals have been proven best when the pulse widths are $0.5/{f_0}$ (${f_0}$ refers to the resonance frequencies of the bending vibrator). However, acoustic logging uses transformers to improve the excitation power, and these transformers change the rectangular excitation signals into similar half-sine signals. We study the relationships between the pulse widths of the similar half-sine excitation signals and the characteristics of the excited acoustic signals. Finite element analyses are performed to investigate the displacements of the center node on the surface of the piezoelectric ceramics that are excited by the pulse signals of different widths. Then, we design a circuit to realise the rectangular and half-sine excitation signals. Subsequently, acoustic experiments are carried out in our sound-deadening water tank to certify the simulation results. Results indicate that the best pulse width is $0.75/{f_0}$.
Designing monitoring networks for local earthquakes
Authors: Nolte Keith A , Tsoflias George P , Holubnyak Yevhen , Raney Jennifer , Wreath Dana
Published: January 2022

Seismic networks are essential for monitoring local earthquakes in connection to industrial activities, including wastewater injection and CO2 sequestration. Because these networks are typically deployed for short periods of time at specific sites, it is beneficial to develop best practices for efficient and effective installation and monitoring. Such standards are available for regional earthquake and microseismic monitoring, but not readily available for local scale (tens of kilometer scale) monitoring. Once the region of interest has been determined, the key parameters for establishing a network are available monitoring station locations, site noise, and site utility. Networks should be designed based on the project monitoring goals for earthquake magnitude and density. Herein, a network was established at the Patterson and Hartland Oil Fields in western Kansas in association with a US Department of Energy CarbonSAFE carbon capture and sequestration research project. We employed observations from an analog local network, the Wellington Earthquake Monitoring Network in south-central Kansas, to assess site noise and estimate earthquake detection thresholds for the Patterson and Hartland fields. Noise from oil production facilities was evaluated, concluding that oil lease sites are suitable for monitoring small local earthquakes (M1-M3). The network was designed to have a magnitude of completeness of M1 while using station locations on existing field operator leases. Fifteen months of continuous network operation demonstrates reliable and efficient local earthquake monitoring and provides best practices recommendations for similar operations.
Assessment of Age, Gender, Mating Status, and Size on Single and Repeat Flight Capabilities of Heilipus lauri Boheman (Coleoptera: Curculionidae)
Authors: Hoddle Mark S , Hoddle Christina D , Milosavljević Ivan , Estrada-Venegas Edith G , Equihua-Martínez Armando
Published: January 2022

Heilipus lauri Boheman (Coleoptera: Curculionidae) is a specialist pest of avocado fruit and is considered an incursion risk for U.S. avocado producers. At the time work reported here was undertaken the flight capabilities of H. lauri were unknown. Consequently, proactive studies were undertaken to quantify aspects of this pest’s flight capabilities to inform potential future control efforts. Flight mill studies were conducted in a quarantine laboratory to measure the dispersal capacity of H. lauri with respect to gender, mating status, and size on the single and repeat flight capabilities of weevils. Gender, mating status, and size did not significantly affect measured flight parameters. Average total distances flown and flight velocity, and mean maximum flight bout distances and durations significantly declined as weevil age increased and when weevils engaged in repeat flights. Survivorship rates were significantly reduced as the number of successive flights undertaken increased. The distribution of total average flight distances flown and total cumulative flight distances flown was platykurtic. The implications of these findings are discussed in terms of developing incursion management plans.
First-line therapy in non-small cell lung cancer patients with EGFR activating mutations: a consideration of the clinical position of osimertinib based on the subset of Japanese patients in the FLAURA study
Authors: Tsukita Yoko , Inoue Akira
Published: January 2022

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been established as the standard first-line treatment for patients with previously untreated advanced non-small cell lung cancer (NSCLC) with an EGFR activating mutation. In the FLAURA study, osimertinib, third-generation EGFR-TKI, resulted in significantly longer progression-free survival and overall survival (OS) than first-generation EGFR-TKIs (gefitinib or erlotinib) in patients with previously untreated advanced NSCLC with an EGFR activating mutation. Osimertinib is now widely used as first-line therapy for those patients. In Japanese subset analysis of the FLAURA study, the median progression-free survival was prolonged by osimertinib (19.1 months) relative to gefitinib (13.8 months). However, there was no apparent OS benefit, albeit at the level of an exploratory post-hoc analysis. Although the safety profile in the Japanese subset was generally consistent with the overall population, the incidence of liver enzyme increases in the gefitinib group and that of interstitial lung disease/pneumonitis in the osimertinib group was higher among Japanese patients. There is now an increasing number of first-line treatment options for NSCLC with EGFR mutations, including EGFR-TKIs in combination with platinum-doublet chemotherapy or anti-angiogenic drugs. These combinations show progression-free survival benefits similar to osimertinib regardless of the mutation type. Therefore, a first-line combination regimen followed by osimertinib remains an attractive strategy. We review data from the randomized clinical trials of first-line EGFR-TKIs including a subset of Japanese patients and discuss first-line therapies for patients with NSCLC harbouring EGFR mutations.
Thematic Analysis of Organizational Characteristics in NCI Community Oncology Research Program Cancer Care Delivery Research
Authors: Weaver Sallie J , Verhoeven Dana C , Castro Kathleen M , Adjei Brenda A , Geiger Ann M
Published: January 2022

Organizational characteristics, including organizational structures and processes, are important to understanding care delivery and health outcomes. However, organizational-level constructs present measurement challenges in care delivery research. This analysis aims to understand if, when, and how organizational characteristics are examined in a National Cancer Institute (NCI) research network conducting cancer care delivery research (CCDR). The NCI Community Oncology Research Program encourages consideration of organizational variables in CCDR studies. We conducted a cross-sectional thematic analysis to identify organizational characteristics examined in this portfolio of research. Organizational characteristics targeted, related measures, and analytic approach were abstracted by 2 study investigators using a coding framework adapted from 2 existing frameworks. A total of 78.9% of eligible study protocols included organizational characteristics. Structural characteristics were the most common, collected in all 15 included protocols, 14 examined at least 1 organizational process, and 12 examined organizational-level outcomes. Most studies proposed descriptive practice-level analyses or multilevel analyses using random effects to account for clustering of patients and staff within practices. Few (n = 5) specified that organizational variables would be modeled as effects of interest (vs covaried out) or proposed analytic approaches that could more robustly examine effects of targeted organizational characteristics on primary outcomes. Inclusion of organizational variables is common in CCDR conducted through the NCI Community Oncology Research Program, NCI’s national network charged with bringing cancer clinical trials to people in their communities. Nonetheless, opportunities remain to improve the use of theory to guide organizational construct selection, operationalization, measurement, and incorporation into study hypotheses and analyses.