bluuebunny/crossref_metadata_2025 huggingface dataset:
C98. The Role of Echocardiography as a Diagnostic Modality in Pulmonary Embolism in Intensive Care
Authors: Alaydrus S Q , Munirwan H
Published: March 2023

Background

Pulmonary embolism (PE) is the third most frequent cause of death in the world. In epidemiological studies, annual incidence rates for PE range from 39-115 per 100 000 population. Acute PE interferes with both circulation and gas exchange. Right ventricular (RV) failure due to acute pressure overload is considered the primary cause of death in severe PE.

Case Summary

A 70-year-old female patient presents to the emergency room of RSUDZA with complaints of typical chest pain that has been experienced since 3.5 hours before admission. In the emergency department, patients with obesity status with a general condition are weak and agitated. Physical examination found within normal limits. From laboratory test, there were leukocytosis and increasing of D-Dimer. From ECG we found McGinn White Sign. Based on echocardiography, we found RV/LV basal ratio > 1 accompanied by Mc Connel sign and decreased right ventricular systolic function.

Discussion

Echocardiography is one of diagnostic modalities that is very useful for making a diagnosis, where the use of echocardiography is more accessible than computer tomography (CT) as the gold standard. In this case, by using echocardiography especially in intensive rooms, the diagnosis of pulmonary embolism can be established faster in high risk patients. The prognosis of pulmonary embolism is very dependent on the speed at which the diagnosis is made.
C99. Torsade de pointes in coronavirus disease 2019 patient: hypopotassemia, cardiac injury, and drug-induced arrhythmia
Authors: Shandy C A , Jayantika I G A B K
Published: March 2023

Background

Coronavirus disease 2019 (COVID-19) is a viral disease with wide spectrum of clinical manifestation. Malignant arrhythmia had been reported, however the exact mechanism remains unclear. We present a case of Torsade de Pointes (TdP) in COVID-19 patient.

Case Description

A 28 years old female, post caesarean section, confirmed COVID-19, was consulted to cardiology department due to acute lung oedema and premature ventricular complex (PVC) bigeminy. Oxygen saturation dropped to 78% with non-rebreathing mask, so she was intubated. She got furosemide and amiodarone drip. Later on, she developed pulseless ventricular tachycardia, TdP. Defibrillation 200 J was done and MgSO4 2 gram intravenous bolus was delivered. The rhythm converted to normal sinus rhythm, with prolonged QT Interval (503 ms). Potassium level was 2.7, hs-troponin I level was 510.6, and IL-6 level was 33.95. Echocardiogram showed global normokinetic with EF 64% on dobutamin. Amiodarone was stopped. She got MgSO4 drip and potassium chloride drip.

Discussion

Cardiac involvement in COVID-19 are common. Possible mechanisms are systemic inflammation and cytokine storm, as shown by increased IL-6. Cardiac injury, marked by increased hs-troponin I, causes abnormal conduction and prolonged repolarization due to interstitial edema and cardiac fibrosis, with abnormal Ca2+ handling and down regulation of K+ channels. These, together with QT-prolonging effect of amiodarone and hypokalemia, hypoxia, or neurohormonal stress, can induce TdP. Early treatment, ECG monitoring, and correcting electrolyte imbalance are very crucial in COVID-19. Once lethal arrhythmia ensues, proper anti-arrhythmia administration and withdrawal of contributing medications can prevent mortality.
C101. Toxoplasmic Myocarditis in Immunocompetent Patient: A Rare Case Report
Authors: Suryawan Willy , Siswanto Bambang Budi , Kurniawan Agnes
Published: March 2023

Background

Toxoplasmosis is the most frequent protozoan infection among human. Primary acquired infections in immuno-competent hosts are usually asymptomatic or may cause only slight, self-resolving and not pathognomonic symptoms. Although often considered as benign, acute infections in young healthy adults can lead to heart inﬂammation, including acute myocarditis.

Case Illustration

A 28-year-old man was admitted to the hospital with a chief complaint of flu-like illness with intermittent fever and sharp chest pain. His physical examination was unremarkable. The electrocardiography showed no significant ST-T changes. His laboratory investigations gave the following results: elevated level of HsTrop T (571 ng/L; reference: <4 ng/dL), SGOT (112 U/L; reference: <41 U/L), SGOT (114 U/L; reference: <41 U/L). The echocardiography showed lateral pericardial thickening with preserved left ventricular function. He underwent cardiac MRI (cMRI). The cMRI showed myocardial edema without ischemic scar. The serological test is positive for recent Toxoplasma infection. Therefore, the patient was diagnosed with acute toxoplasmic myocarditis and subsequently treated with corticosteroid, ACE-I, beta blocker, and a combination of pyrimethamine and clindamycin. His symptoms was improved.

Discussion

We reported a case of an acute toxoplasmic myocarditis in an immunocompetent young man. This case demonstrates the importance of determining the etiology of myocarditis in order to start an appropriate therapy and prevent possible sequeale.
Continuity of primary care among homeless adults with mental illness who received a housing and mental health intervention
Authors: To Matthew J , Mejia-Lancheros Cilia , Lachaud James , Hwang Stephen W
Published: March 2023

Background

Continuity of primary care (CPC) is associated with reduced mortality and improved health status. This study assessed the level of CPC and changes in CPC over 6 years among adults with experience of homelessness and mental illness who received a Housing First intervention.

Methods

Participants were adults (≥18 years old) with a serious mental disorder and experiencing chronic homelessness enrolled between October 2009 and June 2011 in the Toronto site of the Canadian At Home/Chez Soi study and followed until March 2017. Participants were randomized to Housing First with intensive case management (HF-ICM), Housing First with assertive community treatment (HF-ACT), or treatment as usual. For this report, 280 intervention group participants (HF-ICM, n = 193 and HF-ACT, n = 87) were analysed using data from health records. The main outcome was CPC measured by the Continuity of Care Index as a continuous and categorical variable among participants during 3 consecutive 2-year periods.

Results

Most HF-ICM participants had low levels of CPC, with 68%–74% of this group having low CPC across all time periods. Similarly, most HF-ACT participants had low levels of CPC, with 63%–78% of this group having low CPC across all time periods.

Conclusions

Among this group of individuals with mental illness who were experiencing homelessness, CPC remained low over 6 years of follow-up. This study highlights that housing and mental health interventions may need to place greater emphasis on improving CPC using effective strategies that are specifically geared towards this important goal among their clients.
Comprehensive mutation profiling from wastewater in southern Germany extends evidence of circulating SARS-CoV-2 diversity beyond mutations characteristic for Omicron
Authors: Agrawal Shelesh , Orschler Laura , Zachmann Kira , Lackner Susanne
Published: March 2023

Tracking SARS-CoV-2 variants in wastewater is primarily performed by detecting characteristic mutations of the variants. Unlike the Delta variant, the emergence of the Omicron variant and its sublineages as variants of concern has posed a challenge in using characteristic mutations for wastewater surveillance. In this study, we monitored the temporal and spatial variation of SARS-CoV-2 variants by including all the detected mutations and compared whether limiting the analyses to characteristic mutations for variants like Omicron impact the outcomes. We collected 24-hour composite samples from 15 wastewater treatment plants (WWTP) in Hesse and sequenced 164 wastewater samples with a targeted sequencing approach from September 2021 to March 2022. Our results show that comparing the number of all the mutations against the number of the characteristic mutations reveals a different outcome. A different temporal variation was observed for the ORF1a and S gene. As Omicron became dominant, we observed an increase in the overall number of mutations. Based on the characteristic mutations of the SARS-CoV-2 variants, a decreasing trend for the number of ORF1a and S gene mutations was noticed, though the number of known characteristic mutations in both genes is higher in Omicron than Delta.
Multimodal deep learning methods enhance genomic prediction of wheat breeding
Authors: Montesinos-López Abelardo , Rivera Carolina , Pinto Francisco , Piñera Francisco , Gonzalez David , Reynolds Mathew , Pérez-Rodríguez Paulino , Li Huihui , Montesinos-López Osval A , Crossa Jose
Published: March 2023

While several statistical machine learning methods have been developed and studied for assessing the genomic prediction (GP) accuracy of unobserved phenotypes in plant breeding research, few methods have linked genomics and phenomics (imaging). Deep learning (DL) neural networks have been developed to increase the GP accuracy of unobserved phenotypes while simultaneously accounting for the complexity of genotype–environment interaction (GE); however, unlike conventional GP models, DL has not been investigated for when genomics is linked with phenomics. In this study we used 2 wheat data sets (DS1 and DS2) to compare a novel DL method with conventional GP models. Models fitted for DS1 were GBLUP, gradient boosting machine (GBM), support vector regression (SVR) and the DL method. Results indicated that for 1 year, DL provided better GP accuracy than results obtained by the other models. However, GP accuracy obtained for other years indicated that the GBLUP model was slightly superior to the DL. DS2 is comprised only of genomic data from wheat lines tested for 3 years, 2 environments (drought and irrigated) and 2–4 traits. DS2 results showed that when predicting the irrigated environment with the drought environment, DL had higher accuracy than the GBLUP model in all analyzed traits and years. When predicting drought environment with information on the irrigated environment, the DL model and GBLUP model had similar accuracy. The DL method used in this study is novel and presents a strong degree of generalization as several modules can potentially be incorporated and concatenated to produce an output for a multi-input data structure.
Transcriptome profile in Drosophila Kc and S2 embryonic cell lines
Authors: Klonaros Daniel , Dresch Jacqueline M , Drewell Robert A
Published: March 2023

Drosophila melanogaster cell lines are an important resource for a range of studies spanning genomics, molecular genetics, and cell biology. Amongst these valuable lines are Kc167 (Kc) and Schneider 2 (S2) cells, which were originally isolated in the late 1960s from embryonic sources and have been used extensively to investigate a broad spectrum of biological activities including cell–cell signaling and immune system function. Whole-genome tiling microarray analysis of total RNA from these two cell types was performed as part of the modENCODE project over a decade ago and revealed that they share a number of gene expression features. Here, we expand on these earlier studies by using deep-coverage RNA-sequencing approaches to investigate the transcriptional profile in Kc and S2 cells in detail. Comparison of the transcriptomes reveals that ∼75% of the 13,919 annotated genes are expressed at a detectable level in at least one of the cell lines, with the majority of these genes expressed at high levels in both cell lines. Despite the overall similarity of the transcriptional landscape in the two cell types, 2,588 differentially expressed genes are identified. Many of the genes with the largest fold change are known only by their “CG” designations, indicating that the molecular control of Kc and S2 cell identity may be regulated in part by a cohort of relatively uncharacterized genes. Our data also indicate that both cell lines have distinct hemocyte-like identities, but share active signaling pathways and express a number of genes in the network responsible for dorsal–ventral patterning of the early embryo.
Selection and geography shape male reproductive tract transcriptomes in Drosophila melanogaster
Authors: Cridland Julie M , Contino Colin E , Begun David J
Published: March 2023

Transcriptome analysis of several animal clades suggests that male reproductive tract gene expression evolves quickly. However, the factors influencing the abundance and distribution of within-species variation, the ultimate source of interspecific divergence, are poorly known. Drosophila melanogaster, an ancestrally African species that has recently spread throughout the world and colonized the Americas in the last roughly 100 years, exhibits phenotypic and genetic latitudinal clines on multiple continents, consistent with a role for spatially varying selection in shaping its biology. Nevertheless, geographic expression variation in the Americas is poorly described, as is its relationship to African expression variation. Here, we investigate these issues through the analysis of two male reproductive tissue transcriptomes [testis and accessory gland (AG)] in samples from Maine (USA), Panama, and Zambia. We find dramatic differences between these tissues in differential expression between Maine and Panama, with the accessory glands exhibiting abundant expression differentiation and the testis exhibiting very little. Latitudinal expression differentiation appears to be influenced by the selection of Panama expression phenotypes. While the testis shows little latitudinal expression differentiation, it exhibits much greater differentiation than the accessory gland in Zambia vs American population comparisons. Expression differentiation for both tissues is non-randomly distributed across the genome on a chromosome arm scale. Interspecific expression divergence between D. melanogaster and D. simulans is discordant with rates of differentiation between D. melanogaster populations. Strongly heterogeneous expression differentiation across tissues and timescales suggests a complex evolutionary process involving major temporal changes in the way selection influences expression evolution in these organs.
Echoes of Silence: The Politics of Generational Memory in East Germany’s Literary Intelligentsia
Authors: Harsch Donna
Published: March 2023

This article examines family memoirs and novels by children or grandchildren of East Germany’s literary founding generation. Written after reunification, this generational literature looks back on family life in the German Democratic Republic. It paints a group portrait of a distinct milieu in East German society and inside the Communist elite. Shaped by politics, habitus and social background, this milieu was stamped by German history, Jewish history and the history of Communism. A unifying thread runs through this family literature: intense generational dissonance stemming from parental silence about the Nazi past and the socialist present. In children’s memory, parents’ stories about exile clung to a narrative of victorious anti-fascist struggle and left out their suffering as Jews in Nazi-occupied Europe or as Communists in the Stalinist USSR. The article traces the postwar reverberations of silence about the past. Younger generations asked the founding generation who in the family survived, and how, and who did not survive, and why. How, they wondered, could parents condone socialist repression after resisting Nazi terror? Children confronted parental silence emotionally, culturally and politically, in a similar mode, the article argues, to the generational stance of 68ers in West Germany. In their discontent with anti-fascist parents, however, this group of East Germans shared the point of view of youth rebels in non-German Europe who challenged parents who opposed, not supported, National Socialism.
Agency and Mental Health Among Peruvian Older Adults During the COVID-19 Lockdown
Authors: Flores-Flores Oscar , Otero-Oyague Diego , Rey-Evangelista Lorena , Zevallos-Morales Alejandro , Ramos-Bonilla Gabriela , Carrión Ivonne , Patiño Vanessa , Pollard Suzanne L , Parodi Jose F , Hurst John R , Gallo Joseph J , Reynolds Rodney
Published: March 2023

Objectives

To explore the experiences of older Peruvian adults living in urban areas of Lima under lockdown due to the National COVID-19 Emergency, this study analyzes how older adults (aged 60 and older) exercise agency while also living with the negative impacts of coronavirus disease 2019 (COVID-19) and related control measures.

Methods

Between August and December 2020, our research team conducted a telephone-based, qualitative study, in which we undertook semistructured interviews with a purposive sample of low-income older adults living with chronic multimorbidities and limited resources. Forty older adults, 24 women and 16 men, with a mean age of 72 years, participated in the study. For data analysis, we employed thematic analysis with a predominantly inductive approach.

Results

Older adults demonstrated several forms of agency to regulate emotions, maintain crucial bonds, foster social relationships, and seek economic and food security. Older adults experienced entertainment and support by caring for pets, undertaking farm work, and practicing their religious beliefs. For several participants and their families, quarantine was an opportunity to strengthen family relationships and learn new technologies. Older adults and their families reorganized themselves to assume new roles and perform activities that improved self-worth and confidence, thereby improving their well-being and mental health.

Discussion

Peruvian older adults exerted agency in different ways to respond to and sustain their mental health during the COVID-19 lockdown. Policymakers should value and recognize the agency of older adults when planning future health responses.
Psychosocial Care Needs of Women with Breast Cancer: Body Image, Self-Esteem, Optimism, and Sexual Performance and Satisfaction
Authors: Montañés-Muro Pilar , Martínez-Tomé Marina , García-Manzano Guadalupe
Published: March 2023

As breast cancer is on the rise, it is essential to understand the consequences of the diagnosis for patients. This article investigates whether there are differences in different psychosocial variables in Spanish women with breast cancer according to the type of surgery the patients underwent and in comparison with a control group. A study was carried out in the north of Spain in which 54 women participated (27 women were the control group, and 27 women who had been diagnosed with breast cancer). The results of the study indicate that women with breast cancer have lower self-esteem and worse body image, sexual performance, and sexual satisfaction than women in the control group. No differences were found in optimism. These variables do not differ according to the type of surgery the patients underwent. The findings confirm the need to work on these variables in women diagnosed with breast cancer in psychosocial intervention programs.
Risk of Tuberculosis and Hepatitis B Reactivation in Patients With Crohn’s Disease on Ustekinumab: A Nationwide Real-World Study
Authors: Liu Rongbei , Li Zhilun , Ye Lingna , Hu Jing , Tang Jian , Chen Baili , Chen Xiuli , Tan Bei , Gu Yubei , Xie Chen , Ouyang Chunhui , Song Xiaomei , Li Fan , Fan Yanyun , Ren Haixia , Zhu Liangru , Chen Min , Jiang Wenyu , Cao Qian
Published: March 2023

Background

Ustekinumab (UST) was approved in China for moderate-to-severe Crohn’s disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST.

Methods

A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation.

Results

Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up.

Conclusions

UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.
Nature in Focus: The Invisibility and Re-Emergence of Rivers, Land and Animals in Colombia’s Transitional Justice System
Authors: Ariza-Buitrago Isabella , Gómez-Betancur Luisa
Published: March 2023

Harms resulting from a 50-year-old conflict in Colombia were out of all proportion. Clashes between organized armed groups, such as guerillas, army troops and paramilitary groups, resulted in countless human rights violations. The emergence, degradation and continuation of the war has shown that, beyond a clash of armed groups, the conflict was and continues to be underpinned by a ‘logic of dispossession, exploitation, and domination.’ In the shadows of the strife, non-armed actors, such as businesspeople, corporations and politicians, benefited from the war, and participated in land grabbing, forced displacement and the illegal possession of land that historically belonged to Indigenous People, campesino and afro-communities. Along with human bodies as the first territory targeted for dispossession, lands, rivers and animals were severely impacted. This article explains how the Colombian transitional justice architecture – anthropocentric and focused only on armed actors’ accountability – is ill-equipped to deliver justice and remedy for victims of corporate abuse and to properly address the harms against land, rivers and animals. This piece also reflects on the endeavours that both transitional justice institutions themselves and civil society at the domestic and international levels have made to effectively respond to the Colombian conflict’s systems of dispossession and, most importantly, to their victims.
Nipah Virus Bangladesh Infection Elicits Organ-Specific Innate and Inflammatory Responses in the Marmoset Model
Authors: Stevens Christian S , Lowry Jake , Juelich Terry , Atkins Colm , Johnson Kendra , Smith Jennifer K , Panis Maryline , Ikegami Tetsuro , tenOever Benjamin , Freiberg Alexander N , Lee Benhur
Published: March 2023

The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal nonhuman primate (NHP) at high biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all 4 infected marmosets. Three developed pulmonary edema and hemorrhage as well as multifocal hemorrhagic lymphadenopathy, while 1 recapitulated neurologic clinical manifestations and cardiomyopathy on gross pathology. Organ-specific innate and inflammatory responses were characterized by RNA sequencing in 6 different tissues from infected and control marmosets. Notably, a unique transcriptome was revealed in the brainstem of the marmoset exhibiting neurological signs. Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.
Trends in Adolescent Human Papillomavirus Vaccination and Parental Hesitancy in the United States
Authors: White Jodie L , Grabowski M Kate , Rositch Anne F , Gravitt Patti E , Quinn Thomas C , Tobian Aaron A R , Patel Eshan U
Published: March 2023

Background

Human papillomavirus (HPV) vaccination coverage remains suboptimal in the United States, underscoring the importance of monitoring trends in vaccine hesitancy.

Methods

Cross-sectional data from the 2011–2020 National Immunization Survey–Teen were used to assess trends in HPV vaccination initiation among 13–17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy.

Results

Among all sex and race and ethnicity groups, the prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%). Among hesitant parents, “safety concerns” increased in nearly all demographic groups, with the greatest increases observed for non-Hispanic white female and male teens and no change for non-Hispanic black female teens. In 2019–2020, parents of unvaccinated non-Hispanic white teens were least likely to intend on vaccinating their teens, and the most common reason for hesitancy varied by sex and race and ethnicity (eg, “safety concerns” for white teens and “not necessary” for black female teens).

Conclusions

Although HPV vaccination initiation increased over time, a substantial fraction of parents remain hesitant, and trends in their reason varied by sex and race and ethnicity. Health campaigns and clinicians should address vaccine safety and necessity.
“Citizenship Cheaters” before the Law: Reading Fraud-Based Denaturalization in Norway through Lenses of Exceptionalism
Authors: Birkvad Simon Roland
Published: March 2023

For decades, fraud-based denaturalization was hardly used in Norway. In the 2015–2016 “refugee crisis,” however, the right-wing government decided to reinforce efforts to expose “citizenship cheaters.” This article asks how this decision emerged, what arguments the government articulated to legitimize this decision, and how parliament responded. I examine the Norwegian case by reworking Schmitt and Agamben's perspectives on exceptionalism. The executive desire to reduce naturalized citizens to “bare life” illustrates Agamben's logic of exception: their potential exclusion is inscribed in law. Yet, the analysis shows that exceptionalism does not necessarily lead to “bare lives”: denaturalization was mediated through legal, administrative, and democratic procedures. The opposition submitted proposals to tame the executive's denaturalization powers. In responding to criticism, the government relied on three different arguments to legitimize the decision: (1) moralizing and (2) criminalizing fraud, while simultaneously (3) de-politicizing the decision through hyper-legalism. Such reasoning does not suggest the collapse of law and politics, as Agamben envisions, but rather that states formulate exclusionary politics based on formalistic interpretations of law. The article concludes by problematizing Agamben's claim that we are all equally disposed to sovereign violence. I urge to take seriously social categories of difference in developing a political sociology of exceptionalism.
The Poetic as an Aesthetic Category
Authors: Kriegel Uriah
Published: March 2023

Poems are not the only things we sometimes call poetic. We experience as poetic also prose passages, as well as films, music, visual art, and even occurrences in daily life. But what is it exactly for something to be poetic in this wider sense? Discussion of the poetic in this sense is virtually nonexistent in the extant analytic literature. The aim of this article is to get a start on trying to come to grips with this phenomenon—the poetic as an aesthetic category that outruns poetry as an art form. It proposes an initial sketch of an account in terms of the fittingness of certain affective reactions to artworks and other things, reactions featuring notably elements of tenderness and elevation.
Imipenem/cilastatin/relebactam efficacy, safety and probability of target attainment in adults with hospital-acquired or ventilator-associated bacterial pneumonia among patients with baseline renal impairment, normal renal function, and augmented renal clearance
Authors: Roberts Jason A , Nicolau David P , Martin-Loeches Ignacio , Deryke C Andrew , Losada Maria C , Du Jiejun , Patel Munjal , Rizk Matthew L , Paschke Amanda , Chen Luke F
Published: March 2023

Objectives

To assess the relationship between renal function and efficacy/safety of imipenem/cilastatin/relebactam for the treatment of hospital-acquired/ventilator-associated pneumonia (HABP/VABP) from RESTORE-IMI 2 and determine the PTA.

Methods

Adults with HABP/VABP were randomized 1:1 to IV imipenem/cilastatin/relebactam 1.25 g or piperacillin/tazobactam 4.5 g every 6 h for 7–14 days. Initial doses were selected by CLCR and adjusted thereafter, as appropriate. Outcomes included Day 28 all-cause mortality (ACM), clinical response, microbiological response and adverse events. Population pharmacokinetic modelling and Monte Carlo simulations assessed PTA.

Results

The modified ITT population comprised those with normal renal function (n = 188), augmented renal clearance (ARC; n = 88), mild renal impairment (RI; n = 124), moderate RI (n = 109) and severe RI (n = 22). ACM rates were comparable between treatment arms among all baseline renal function categories. Clinical response rates were comparable between treatment arms for participants with RI and normal renal function but were higher (91.7% versus 44.4%) for imipenem/cilastatin/relebactam-treated versus piperacillin/tazobactam-treated participants with CLCR ≥250 mL/min (n = 21). Microbiologic response rates were comparable between treatment arms for participants with RI but higher among those treated with imipenem/cilastatin/relebactam in participants with CLCR ≥90 mL/min (86.6% versus 67.2%). Adverse events were comparable between treatment arms across renal function categories. Joint PTA was >98% for key pathogen MICs for susceptible pathogens (MIC ≤2 mg/L).

Conclusions

Prescribing information–defined dose adjustments in participants with baseline RI and full dosing of imipenem/cilastatin/relebactam 1.25 g every 6 h for participants with normal renal function or augmented renal clearance achieved sufficiently high drug exposures and favourable safety and efficacy profiles.
What Explains the Firm Size Distribution in Sub-Saharan Africa and Why Does It Matter?
Authors: Teal Francis
Published: March 2023

In this issue of the Journal of African Economies we publish two papers concerned with the firm size distribution of manufacturing firms in Sub-Saharan Africa (SSA). One paper examines the changes in the firm size distribution for Ghana, Teal (this issue), the other for Ethiopia, Azmete et al. (this issue). This note is intended to introduce, and compare, the findings of these two papers and to place those findings in the wider policy debate as to what explains the performance of the manufacturing sector in SSA.
Clinical Validation of the sFlt-1:PlGF Ratio as a Biomarker for Preeclampsia Diagnosis in a High-Risk Obstetrics Unit
Authors: Miller Jessica J , Higgins Victoria , Melamed Nir , Hladunewich Michelle , Ma Liyan , Yip Paul M , Fu Lei
Published: March 2023

Background

Preeclampsia is a multisystem disorder defined by new onset of hypertension with proteinuria after 20 weeks gestation. In part due to dysregulation of pro-angiogenic factors (e.g., placental growth factor [PlGF]) and anti-angiogenic factors (e.g., soluble fms-like tyrosine kinase 1 [sFlt-1]), preeclampsia results in decreased placental perfusion. An increased sFlt-1:PlGF ratio is associated with increased risk of preeclampsia. In this study, we evaluated sFlt-1:PlGF cutoffs and evaluated the clinical performance of sFlt-1:PlGF for predicting preeclampsia.

Methods

sFlt-1:PlGF results from 130 pregnant females with clinical suspicion of preeclampsia were used to evaluate the diagnostic accuracy of different sFlt-1:PlGF cutoffs and to compare the clinical performance of sFlt-1:PlGF to traditional preeclampsia markers (proteinuria and hypertension). Serum sFlt-1 and PlGF were measured using Elecsys immunoassays (Roche Diagnostics) and preeclampsia diagnosis was verified by expert chart review.

Results

A sFlt-1:PlGF cutoff of >38 yielded the greatest diagnostic accuracy of 90.8% (95% CI, 85.8%–95.7%). Using a cutoff of >38, sFlt-1:PlGF exhibited a greater diagnostic accuracy than traditionally used parameters such as new or worsening proteinuria or hypertension (71.9% and 68.6%, respectively). sFlt-1:PlGF >38 exhibited a negative predictive value (NPV) of 96.4% for rule-out of preeclampsia within 7 days, and a positive predictive value (PPV) of 84.8% for predicting preeclampsia within 28 days.

Conclusions

Our study shows the superior clinical performance of sFlt-1:PlGF over hypertension and proteinuria alone to predict preeclampsia at a high-risk obstetrical unit.
Fine characterization and microbiota assessment as keys to understanding the positive effect of standardized natural citrus extract on broiler chickens
Authors: Cisse Sekhou , Bahut Muriel , Marais Coralie , Zemb Olivier , Chicoteau Pierre , Benarbia Mohammed El Amine , Guilet David
Published: March 2023

The objective of this study was to investigate the effect and composition of a standardized natural citrus extract (SNCE) on both broiler chickens’ growth performances and intestinal microbiota. A total of 930 one-day-old males were randomly assigned to three dietary treatments: a control treatment (CTL) in which broiler chickens were fed with a standard diet and two citrus treatments in which broiler chickens were fed with the same standard diet supplemented with 250 ppm and 2,500 ppm of SNCE, respectively. Each dietary treatment was composed of 10 experimental units (pen) of 31 broiler chickens each. Growth performances such as feed consumption, body weight, and feed conversion ratio (FCR) were recorded weekly until day 42. Litter quality was also weekly recorded while mortality was daily recorded. One broiler chicken was randomly selected from each pen (10 chickens/group) and ceca samples were collected for microbiota analysis at day 7 and 42. Chromatographic methods were used to determine molecules that enter into the composition of the SNCE. Results from the characterization of SNCE allowed to identify pectic oligosaccharides (POS) as a major component of the SNCE. In addition, 35 secondary metabolites, including eriocitrin, hesperidin, and naringin, were identified. The experiment performed on broiler chickens showed that the final body weight of broiler chickens fed diets supplemented with SNCE was higher than those fed the CTL diets (P < 0.01). Broiler cecal microbiota was impacted by age (P < 0.01) but not by the dietary supplementation of SNCE. Results indicate that SNCE allowed enhancing chickens’ performances without any modulation of the cecal microbiota of broiler chickens. The characterization of SNCE allowed to identify compounds such as eriocitrin, naringin, hesperidin, and POS. Thus, opening new horizons for a better understanding of the observed effect on broiler chickens’ growth performances.
A32 PHAGE TREATMENT DELAYS ONSET OF CROHN’S-ASSOCIATED E. COLI DRIVEN COLITIS IN MICE COLONIZED WITH A DEFINED MICROBIOTA
Authors: Jackson K , Galipeau H , Hann A , Coombes B , Hosseinidoust Z , Verdu E
Published: March 2023

Background

Opportunistic pathogens have been postulated to drive dysregulated inflammation in inflammatory bowel disease (IBD). Indeed, adherent-invasive Escherichia coli (AIEC) isolated from IBD patients have pathobiont and pro-inflammatory characteristics. Current treatments for IBD suppress the immune response and do not target key microbial drivers, therefore novel strategies are required.

Purpose

Our aim was to determine whether bacteriophage therapy targeted against AIEC could reduce the severity of E. coli-driven colitis in gnotobiotic mice.

Method

Adult germ-free C57BL/6 mice were colonized with altered Schaedler-like flora (ASF) and E. coli NRG857c, a Crohn’s disease-associated bacterial isolate. Three weeks later, mice were treated with daily phage (selected by killing curves bioassays against E. coli NRG857c) or PBS for 2 weeks (n=6/group). Mice were then exposed to low-dose dextran sulfate sodium (2%; DSS) in drinking water for 5 days, followed by 2 days of water. PBS-treated mice (n=6) that received no DSS were used as additional negative controls. Mice were monitored daily for weight, stool consistency, and occult blood. At sacrifice, colon tissue was collected for histological analysis and fecal contents were cultured to determine bacterial load. In separate experiments, C57BL/6NTac-Il10em8Tac (IL-10-/-) mice were colonized with ASF-like microbiota and E. coli NRG857c. Three weeks later, mice (n=5) were treated with weekly phage or PBS (n=5) for 7 weeks. Mice were monitored weekly as described above.

Result(s)

Daily phage treatment reduced the severity of clinical symptoms induced by acute DSS administration (p < 0.001 vs. DSS-PBS treated mice). At endpoint, phage treatment was associated with lower histological scores as compared with DSS-PBS controls (p < 0.0001). A 1-log reduction in AIEC bacterial load was observed in phage treated mice as compared with DSS-PBS controls (p < 0.001). In IL-10-/- mice, weekly phage treatment delayed the spontaneous onset of colitis (p < 0.0001 vs. PBS-treated mice). At endpoint, mice treated with phage had lower colitis scores. Reduced weekly AIEC bacterial load was observed in phage-treated mice.

Conclusion(s)

Lytic phages, targeting a known AIEC pathobiont isolated from Crohn’s disease patients, ameliorate acute intestinal injury and delay onset of spontaneous colitis. Future work will investigate the mechanisms by which phage therapy prevents and treats colitis, to better inform clinical trial design.

Disclosure of Interest

None Declared
Is salt the solution? Interactions between trace-metal uptake and salinity in the freshwater crabPotamonautes warreniCalman, 1918 (Decapoda: Brachyura: Potamonautidae)
Authors: Glendinning Susan K , Vosloo Andre
Published: March 2023

Crustaceans inhabiting freshwater are more vulnerable to increased loading with dissolved trace metals than those from more saline conditions for both physicochemical and physiological reasons. Potamonautes warreni (Calman, 1918) is a true freshwater crab inhabiting rivers in proximity to mining activities in South Africa. In order to assess whether the uptake of zinc (Zn2+) and cadmium (Cd2+) were associated with Na+- and Ca2+-uptake routes, individuals of P. warreni were acclimated to different Na+ or Ca2+ concentrations before measuring trace-metal uptake into the haemolymph and tissues in an intermediate freshwater. Cd2+ uptake into the haemolymph was elevated following acclimation to ‘Na+ replete’ conditions, when compared with ‘Na+ deplete’ conditions, indicating that a physiological response to the acclimation salinity had influenced Cd2+ uptake. Zn2+ uptake by the whole body was elevated in P. warreni individuals from the ‘Na+ replete’ group when compared with crabs acclimated to Na+ free water. A general change in permeability may have occurred and indeed, the apparent water permeability (water efflux) of P. warreni was increased in elevated Na+ and Ca2+ concentrations compared with that in softer water. A comparison of the osmoregulatory ability between P. warreni and the catadromous crab Eriocheir sinensisH. Milne Edwards, 1853 highlighted the greater permeability of the latter. Lower Zn2+ and Cd2+ uptake rates were measured in P. warreni in comparison to those measured in E. sinensis by other authors, indicating that the more well adapted a species is to life in freshwater, the less susceptible they will be to metal uptake. Future investigations to understand further the mechanisms influencing Zn2+ and Cd2+ uptake are required to understand the role that salinity can play in protecting a species from trace-metals released into the environment.
Laboratory evaluations of biodegradable boric acid hydrogel baits for the control of Argentine ant (Hymenoptera: Formicidae)
Authors: Le Benning , Park Hoeun , Campbell Kathleen , Rust Michael K , Lee Chow-Yang , Choe Dong-Hwan
Published: March 2023

Due to their mutualistic relationship with plant pests, the Argentine ant is considered a major pest in subtropical fruit orchards and vineyards. Besides insecticide sprays, liquid baiting has been demonstrated as an effective method to suppress the Argentine ant populations. To improve the economic feasibility of liquid baiting, hydrogel materials have been recently tested as a carrier for liquid baits containing various insecticidal active ingredients. Here, we tested boric acid as a toxicant in the aqueous sugar bait delivered in a biodegradable calcium alginate hydrogel. Laboratory tests demonstrated that boric acid (1%) liquid bait incorporated in the calcium alginate hydrogel effectively killed Argentine ant workers. Potassium sorbate (0.25%) added to the liquid bait as a preservative did not impact the efficacy of boric acid even though it significantly reduced the degree of swelling of the hydrogel beads in the bait solution. Testing with 2-month-old bait suggested that long-term storage might impact bait efficacy even with potassium sorbate preservative.
A chromosome-scale high-contiguity genome assembly of the cheetah (Acinonyx jubatus)
Authors: Winter Sven , Meißner René , Greve Carola , Ben Hamadou Alexander , Horin Petr , Prost Stefan , Burger Pamela A
Published: March 2023

The cheetah (Acinonyx jubatus, SCHREBER 1775) is a large felid and is considered the fastest land animal. Historically, it inhabited open grassland across Africa, the Arabian Peninsula, and southwestern Asia; however, only small and fragmented populations remain today. Here, we present a de novo genome assembly of the cheetah based on PacBio continuous long reads and Hi-C proximity ligation data. The final assembly (VMU_Ajub_asm_v1.0) has a total length of 2.38 Gb, of which 99.7% are anchored into the expected 19 chromosome-scale scaffolds. The contig and scaffold N50 values of 96.8 Mb and 144.4 Mb, respectively, a BUSCO completeness of 95.4% and a k-mer completeness of 98.4%, emphasize the high quality of the assembly. Furthermore, annotation of the assembly identified 23,622 genes and a repeat content of 40.4%. This new highly contiguous and chromosome-scale assembly will greatly benefit conservation and evolutionary genomic analyses and will be a valuable resource, e.g., to gain a detailed understanding of the function and diversity of immune response genes in felids.
The revised reference genome of the leopard gecko (Eublepharis macularius) provides insight into the considerations of genome phasing and assembly
Authors: Pinto Brendan J , Gamble Tony , Smith Chase H , Keating Shannon E , Havird Justin C , Chiari Ylenia
Published: March 2023

Genomic resources across squamate reptiles (lizards and snakes) have lagged behind other vertebrate systems and high-quality reference genomes remain scarce. Of the 23 chromosome-scale reference genomes across the order, only 12 of the ~60 squamate families are represented. Within geckos (infraorder Gekkota), a species-rich clade of lizards, chromosome-level genomes are exceptionally sparse representing only two of the seven extant families. Using the latest advances in genome sequencing and assembly methods, we generated one of the highest-quality squamate genomes to date for the leopard gecko, Eublepharis macularius (Eublepharidae). We compared this assembly to the previous, short-read only, E. macularius reference genome published in 2016 and examined potential factors within the assembly influencing contiguity of genome assemblies using PacBio HiFi data. Briefly, the read N50 of the PacBio HiFi reads generated for this study was equal to the contig N50 of the previous E. macularius reference genome at 20.4 kilobases. The HiFi reads were assembled into a total of 132 contigs, which was further scaffolded using HiC data into 75 total sequences representing all 19 chromosomes. We identified 9 of the 19 chromosomal scaffolds were assembled as a near-single contig, whereas the other 10 chromosomes were each scaffolded together from multiple contigs. We qualitatively identified that the percent repeat content within a chromosome broadly affects its assembly contiguity prior to scaffolding. This genome assembly signifies a new age for squamate genomics where high-quality reference genomes rivaling some of the best vertebrate genome assemblies can be generated for a fraction of previous cost estimates. This new E. macularius reference assembly is available on NCBI at JAOPLA010000000.
A direct numerical simulation method for solid-solid collision and coupling with fluid
Authors: Yang Ming , Liu Jubao , Ding Yuqi , Yue Qianbei , Zhang Qiang
Published: March 2023

The collision between solids in fluid is common in engineering, but the numerical simulation method is less studied. A direct numerical simulation method combining the sharp interface immersed boundary method and the finite element method based on penalty function was established for solid–solid collision and coupling with fluid. The lubrication model for cylinder structures with and without fluid flow was developed using the data regression method. The partitioned coupling algorithm was used to realize the coupling solution between the fluid and solid domains. Four numerical examples were presented to demonstrate the validity of the established method. The numerical simulation of the vortex-induced collisions between two side-by-side cylinders showed the capabilities of the proposed method.
‘Refugee Education Is Our Responsibility’: How Governance Shapes the Politics of Bridging the Humanitarian—Development Divide
Authors: Carvalho Shelby , Haybano Alebachew Kemisso
Published: March 2023

Reforms striving to bridge the humanitarian–development divide in refugee-hosting countries can alter the status quo related to refugee management and service provision. Such changes can result in obstacles to sustainable refugee inclusion when they challenge vested interests. In this paper, we propose a theoretical framework outlining the conditions under which government bureaucracies are likely to cooperate in donor-initiated refugee integration reforms as well as when and how they resist with a focus on the role of governance structures. We draw on archival data, observation, and key informant interviews to apply our framework to the case of Ethiopia as the government and international partners engage in reform efforts to include refugees in the national education system and to move from a humanitarian- to development-oriented model of financing. In this case, we find that reforms backed by international donors fundamentally challenged the vested interests of existing bureaucracies and that the resulting resistance substantially narrowed the original policy goals and will likely have implications for bridging the humanitarian–development divide going forward.